Single trace multi-channel low coherence interferometric sensor

ABSTRACT

Interferometers and autocorrelator based sensors are disclosed that are configured to have multiple sample arms which can be scanned and the backscattered low coherence source light from a sample resolved in a single sweep of one or more variable delays of the sensor. Borescopes and catheters capable of scanning multiple sections or areas of materials and tissues using these sensors are described.

BACKGROUND AND SUMMARY

In various fields of medicine and engineering it is often necessary toinspect surfaces that are difficult to reach. For example enginecylinders, compressors for jet aircraft engines, heat exchangers,internal organs, cavities, and arterial passageways in a patient.Biomedical imaging technology, for example, magnetic resonance imaging,X-ray computed tomography, ultrasound, and confocal microscopy can beused to inspect and characterize a variety of tissues and organs.However, there are many situations where existing biomedical diagnosticsare not adequate. This is particularly true where high resolution, about1 micron, imaging is required. Resolution at this level often requiresbiopsy and histopathologic examination. While such examinations areamong the most powerful medical diagnostic techniques, they are invasiveand can be time consuming and costly. Furthermore, in many situationsconventional excisional biopsy is not possible. Coronary artery disease,a leading cause of morbidity and mortality, is one important example ofa disease where conventional diagnostic excisional biopsy can not beperformed. There are many other examples where biopsy can not beperformed or conventional imaging techniques lack the sensitivity andresolution for definitive diagnosis.

A borescope is an optical device such as a prism or optical fiber thatcan be used to inspect inaccessible spaces. An endoscope is aninstrument for visualizing the interior of a hollow organ like a colonor esophagus. The observed part of the internal surface can beilluminated with the help of the illumination channel and the opticalobservation system allows investigation of the internal space surface.During inspection it may be advantageous and important to investigatelateral surface in the space.

Elements allowing a change in the direction of optical observationpermit inspection inside spaces and lateral surfaces that a rigidborescope or endoscope cannot view. Endoscopes and borescopes caninclude a means of articulating the tip of the scope so that it bends inseveral directions to look around a cavity. However, in manyapplications, for example arteries, there is insufficient room in thecavity or conduit for articulation of the scope tip.

Rather than being flexible, a rigid endoscope can contain a mount, anoptical system for observation, and a light guide. The mount and thelight guide can be placed in a tube housing. The optical axes of theobservation and illumination system for lateral direction are deflectedat an angle with respect to the lens optical axis with the help of aprism. In order to observe the entire lateral surface along the wholetransverse perimeter of the investigated cavity, it is necessary torotate the entire endoscope housing around the axis of symmetry. Fiberoptic inspection devices may contains a lens in a mount and illuminationlamps installed in a housing in a lateral wall of the housing in which awindow is provided. Lateral observation can be performed due to areflection prism situated opposite the window. For panoramic observationof the walls in a space the entire housing needs to be rotated. In someinstruments the illumination source must also be rotated complicatingthe design and operation of such a device.

Current methods for screening and diagnosis of pathologic conditions intissue such as cancer often involve surgical biopsy of the tissuefollowed by histological evaluation. This procedure is not onlyinvasive, time-consuming and expensive but often is not capable of rapidand reliable screening of a large surface such as the colon, esophagus,or stomach. Since early diagnosis and treatment tend to be critical toeffective and successful treatment of these pathologies, the developmentof better techniques and devices for diagnosis and screening wouldresult in improved clinical outcomes.

Optical coherence tomography (OCT) is an imaging technique which allowshigh resolution observation and characterization of tissuemicrostructure imaging with resolution on the order of microns. Thistechnique measures detailed changes within a few millimeters of anon-transparent tissue structure. One drawback of the OCT imaging is thetime required to obtain images over a sufficient area.

Optical coherence domain reflectometry (“OCDR”) is an optical techniquethat uses a scanning Michelson interferometer in conjunction with abroadband illuminating source and cross-correlation detection. Thesimilar technique of optical coherence tomography (“OCT”) can be usedfor imaging with catheters.

Both OCDR and OCT use optical data collected by a single mode opticalfiber to determine the morphology, physical properties and location ofvarious types of interspersed materials or biological tissue. Typicallya probe used in conjunction with either OCDR and OCT includes an opticalfiber having a head at its distal tip. Alternatively, the probe isformed by inserting an optical fiber concentrically into a thin-wallflexible hypodermic stainless-steel tube and fastening it with cement. Awindow in the tube allows light to pass to and from the head at the tipof the optical fiber. The probe is then inserted into the tissue ororgan to be examined. Light emitted by the head of the optical fiber isreflected from the adjacent body of tissue or organ. The head thencollects the reflected light, also known as “back-scattered” light.

Using a Michelson interferometer in conjunction with this apparatus themorphology, properties and location of the various materials, tissue ororgan elements that caused the back-scattered light are determined andan image generated to provide a real-time visual display of the device,body of tissue, or organ being examined.

However, as a typical optical fiber can only emit light and gatherback-scattered light along its axial centerline, it is limited toviewing straight ahead. A view transverse to the axial centerline of thefiber can be obtained by turning or bending the head of the fiberperpendicular to its axial centerline, and this is often very difficultor even impossible in the close confines typically encountered duringsurgical procedures, or in examining the sides of an artery or vein.

Mounting a gradient refractive index lens or a mirrored corner cube onthe head of the optical fiber can be used to obtain lateral scans. Botha gradient refractive index lens or a mirrored corner cube deflect theemitted light at an angle transverse to the axial centerline of theoptical fiber, and thus provide for lateral viewing. However, theseapparatus add bulk to the head of the optical fiber. For example, thediameter of an optical fiber typically used in conjunction with OCDR andOCT is on the order of about 90 microns, while the diameter of thesmallest GRIN lens is about 150 microns and that of the smallestmirrored corner cube is about 125 microns. The use of either of theaforementioned optical devices thus renders some locations inaccessibleand makes the optical fiber more difficult to maneuver. In addition,extremely small GRIN lenses and mirrored corner cubes are quiteexpensive, and very fragile. Their use thus adds to the cost of theprobe, and renders it prone to malfunction.

Embodiments of the present invention are devices that include two ormore sample arms and one or more variable delay reference arms, thedistal ends of the sample arms collecting source light backscatteredfrom a sample. The backscattered light collected by the distal end ofeach sample or sensing arm is combined with reference light and lowcoherence interferometric signals for each sample arm produced in asingle sweep of a variable delay of the device. The interference signalproduced by the interaction of reference light and backscattered lightfor each sample arm is measured by a detector. Optionally the one ormore sample arms have an adjustable delay. The devices of the presentinvention may be used to characterize a material using of low coherencelight backscattered from the sample. These devices eliminate the needfor optical switches or rotatable structures to sequentially addressindependent sample arms and permit the collection of low coherencesource light backscattered from several different samples or fromseveral different locations on a single sample utilizing a single sweepof one or more adjustable delays. The interference signals from deviceprovides information on multiple surfaces of a sample and can be used todiscriminate between healthy and diseased tissue without the need forrotating the probe or translating mirrors within the probe.

In one version of the device, two or more sensing or sample arms of aninterferometer are coupled to one or more reference arms. The device canbe used to obtain the low coherence interferometric (LCI) signals fromall of the sample arms in a single long trace or sweep of one or morereference arms; each reference arm has a variable or adjustable delay.Optionally the sample arms may include an adjustable delay. Theintensity of interference between the backscattered light from thesample and light from the reference section can be measured by adetector coupled to the reference arms and sample arms.

Another version the device is a sensor that includes two or more sensingarms, and a reference section with two or more arms where each referencearm has an adjustable delay. The sensing arms and the reference armsection are capable of being coupled to one or more low coherence lightsources. The reference section and sample arms are configured to resolveinterference of backscattered light and reference light from the two ormore sensing arms in a single trace or sweep of the variable delay ofthe reference section. Optionally each sensing arms has an adjustabledelay. The sample and reference arms can be configured in a relationshipthat permits acquisition of backscattering information from a sample andthat can be used to improve signal averaging and noise reduction.

In another version of the device, two or more combined reference andsensing arms or probes of an autocorrelator are coupled with a delaycompensator having a variable delay. LCI signals from interferencebetween backscatter light collected by the probes and reference lightfrom the probes can be separated or resolved during a single sweep ofthe delay compensator. The probe and delay compensator can be configuredin a relationship that permits acquisition of backscattering informationfrom a sample and that can be used to improve signal averaging and noisereduction. Optionally, each probe arm has an adjustable delay. Theintensity of interference between the backscattered light and referencelight can be measured by a detector coupled to the delay compensatorsection.

The devices of the present invention may include one or more lowcoherence light sources or they can be coupled to one or moreexchangeable or pre- existing low coherence light sources. Optionally,the devices may be used for monitoring and delivering photodynamictherapy to a tissue. An activating light source may be coupled into thesample or probe arms of the devices for photodynamic therapy of atissue. The sensor device may include a detector or it can be connectedto an existing detector to measure the intensity of interference betweenthe reference section light and backscattered light. The detector caninclude or may be connected to a processor that provides an outputproportional to the interference between the backscattered light andreference arm light for each sensing or sample arm.

The sensors and apparatus in various versions of the invention can beincluded in a variety of inspection devices including but not limited toa borescope, endoscope, or catheter probe where the interference signalsfrom the sensor provide simultaneously, information on the surface ofthe of the sample, and more preferable the sensor can discriminatebetween healthy and diseased tissue For example, an apparatus caninclude a guidewire, two or more light propagating probes in proximity,such as surrounding or being enclosed by, the guidewire. The probespropagate low coherence source light from a coupler or circulator intothe sample and propagate backscattered light from the sample back to thecoupler or circulator. The probes are coupled to interferometer or delaycompensator that permits resolution of low coherence interferometricsignals from one or more of the probes in a single scan of theadjustable delay in the compensator. An optical head that can directsource light to the sample in a variety of directions can be positionedon the distal end of the device; the optical head also collectsbackscattered light from the sample.

The device can include probes that guide or propagate light and mayinclude waveguides, optical fibers, or a combination of these. Inaddition the probes can include an internal reflector. In a variousembodiments the reference arm or delay arms are located along with thedetector and processor separately (remotely) from the sample or probearms.

The various sensors and apparatus of the invention can be used tocharacterize objects, tissues, and material samples. The method includescontacting the material(s) with a sensor having two or more probe orsample arms. Each probe arm of the sensor can have an adjustable delay,the probe arms and reference section or interferometer coupled togetherand configured such that an interference between backscattered sourcelight from the sample for two or more probe arms and reference light areresolved during a single trace of one or more variable delays of thedevice. Interference between backscattered source light from each probearm and reference section light in a single trace of the reference armis used to characterize the material.

Preferably the low coherence interferometric signals from the two ormore sample or probe arm are separated from each other by an amount thatpermits at least partial sampling of a material or tissue into two ormore areas or regions. Preferably there is complete separation of thelow coherence interferometric signals from each of the sample or probearms, however incomplete resolution may also be useful in characterizinga material. In one embodiment, the interference detected for each of thetwo or more probes provides a characterization of the material. Forexample the interference may be used to characterize the repair ofdamaged tissue following surgery, the detection of a disease state of atissue, or the presence of debris in a compressor or conduit. Apreferred version of the invention is to use the apparatus to detectvulnerable plaque in a patient.

Because the devices of the present invention are capable of resolvinglow coherence interferometric signals that result from backscatteredlight collected by multiple sample arms in a single trace of anadjustable delay, the invention advantageously eliminates the need foroptical switches to resolve LCI signals from multiple sample arms andeliminates the need for the use of multiple interferometers. Inapplications requiring the collection of several LCI traces in a shortperiod of time, either from a single region or from several regions ordirections, the collection of multiple information in a single tracewill reduce the time for data collection and interpretation. Forexample, in probing the circumference of an artery, a single trace willenable rapid identification of a radial position with vulnerable plaqueas compared with healthy tissue, and enable selection of probing regionsalong that radial position only. The identification can be done bycomparing the various components of a trace, addition and orsubtraction, to quickly determine differences, common features, andprovide diagnosis.

Because the sample arms and probe arms, as well as reference arms anddelay compensators in versions of the invention can be coupled toexisting low coherence light sources, detectors, and processors, thefabrication of removable, interchangeable, or configurable sensordevices is possible.

FIGURES

FIG. 1 is an illustration of an all fiber Michelson LCI interferometerwith associated electronics; in the Michelson interferometer, theoptical delay in the reference arm can be adjusted by means of themotion of a movable mirror or reflector, or by stretching the length ofthe arm using a piezoelectric stretcher;

FIG. 2 is an illustration of the depth dependence of the sensing signalI_(s)(z) for a skin tissue sample.

FIG. 3( a) Is a plot of G(Δ₁) versus Δ₁ illustrating the function ofG(Δ₁) as a coherence gate, (b) is a plot of G(Δ₁)cos(2πΔ₁/λ_(o)) versusΔ₁ illustrating an interference signal gated by G(Δ₁).

FIG. 4 Is an illustration of a Michelson based interferometer withmultiple adjustable delay sensing arms whose interference with referencearm light can be resolved in a single trace of the reference armvariable delay, the sensing arms are shown in contact with a samplematerial having index of refraction n_(s) and light penetration z, themultiple-arm probe can be joined together by means of the tree coupler;

FIG. 5 is an example of a interference signal trace showing the relationamong the various delays elements (L₁, L₂, z_(max)) used to resolve thevarious interference signals I_(1s)(z), I_(2s)(z) and other LCIcomponents of a multiprobe system.

FIG. 6 Illustrates an autocorrelator where each waveguide or probeprovides both the reference signal and the backscattered signal. Thereference signal is a portion of the source light reflected light fromthe partial reflector, and the backscattered signal is the lighttransmitted through L₁ and recaptured at the tip of L₁ afterbackscattering from the sample. The portion of the probe on the left ofthe partial reflector carries both the reference and backscatteredlights traveling backward toward the circulator. The delay between thereference and backscattered light is normally much larger than thecoherence length of the light source, and the two do not interfere. Thedelay compensator has a variable delay that is used to make up for thereference/backscatter delay and bring the two under the coherence gate.

FIG. 7 Illustrates a version of the invention including two or moreprobes arms capable of being coupled to a low coherence light source,each probe arm propagating reference light and propagating backscatteredlight from the sample, each probe partially reflecting the source light.The device includes a delay compensator or interferometer section havingtwo arms that receives reference and backscattered light from the probearms. The delay compensator has polarization maintaining reflectors anda variable delay for each of the arms that is capable of bringinginterference between the reference light and backscattered light (bringsthe reference and backscattered light to within the coherence length ofthe light source); the two or more partially reflecting probes are shownwith an optional adjustable delay and are illustrated in contact with asample, the probe arms are coupled through a circulator withpolarization maintaining adjustable delay arms;

FIG. 8( a) illustrates a side view of a multiple-branch catheter probehaving a biocompatible guide wire enclosing one or more probes, FIG. 8(b) illustrates a cross section of the multiple catheter probe of (a)showing six waveguides or heads, and FIG. 8( c) depicts a traceillustrating the detection of a vulnerable plaque by one of the probes,(probe (3) shown in FIG. 8( b)).

FIG. 9( a) illustrates a side view of a multiple branch catheter probewhere the probes surround all or a portion of the guide wire; FIG. 9( b)illustrates a cross section view of the assembly in (a) having the thinguide wire inside the probe fiber bundle and further illustrating theuse a heat-shrinkable latex or other biocompatible tubing around theprobe bundle.

FIG. 10( a-d) illustrate various catheter head designs forinterferometers and autocorrelators using flat-tip fibers and prismreflectors;

FIG. 11 Illustrates head design for interferometer (a) andautocorrelator (b) using angled-tip fibers.

FIG. 12( a-d) illustrate various non-limiting configurations for probescontaining three to six fiber branches.

FIG. 13. Illustrates a dual reference arm embodiment of a multiple probeinterferometer. The multiple reference arms may be used to achieve LCIsignal averaging and noise reduction.

FIG. 14 is an illustration of a version of the present invention capableof being connected or coupled through waveguides to a low coherencelight source, a detector and a processor.

FIG. 15 is an illustration of a version of the invention that may beused to characterize tissue; the device can be coupled throughwaveguides to multiple wavelength low-coherence sources and coupled to alight source for activating a pharmaceutical agent in contact with thetissue.

FIG. 16 illustrates versions of the invention having waveguides inside ahousing and having a collimator sleeve, or individual collimators, fordirecting low coherence light to a sample and collecting backscatteredlight from the sample.

DETAILED DESCRIPTION

Before the present compositions and methods are described, it is to beunderstood that this invention is not limited to the particularmolecules, compositions, methodologies or protocols described, as thesemay vary. It is also to be understood that the terminology used in thedescription is for the purpose of describing the particular versions orembodiments only, and is not intended to limit the scope of the presentinvention which will be limited only by the appended claims.

It must also be noted that as used herein and in the appended claims,the singular forms “a”, “an”, and “the” include plural reference unlessthe context clearly dictates otherwise. Thus, for example, reference toa “delay” is a reference to one or more optical delays and equivalentsthereof known to those skilled in the art, and so forth. Unless definedotherwise, all technical and scientific terms used herein have the samemeanings as commonly understood by one of ordinary skill in the art.Although any methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of embodimentsof the present invention, the preferred methods, devices, and materialsare now described. All publications mentioned herein are incorporated byreference. Nothing herein is to be construed as an admission that theinvention is not entitled to antedate such disclosure by virtue of priorinvention.

“Optional” or “optionally” means that the subsequently describedstructure, event or circumstance may or may not occur, and that thedescription includes instances where the event occurs and instanceswhere it does not.

Embodiments of the present invention include devices that can have twoor more sample arms and one or more variable delay reference arms, thedistal ends of the sample arms collecting source light backscatteredfrom a sample. The backscattered light collected by the distal end ofeach sample arm is combined with reference light and low coherenceinterferometric signals for each sample arm produced in a single sweepof a variable delay of the device. The interference signal produced bythe interaction of reference light and backscattered light for eachsample arm can be measured by a detector. Optionally the one or moresample arms have an adjustable delay. The devices of the presentinvention may be used to characterize a material based on theinterference between reference light and low coherence lightbackscattered from the sample. These devices eliminate the need foroptical switches or rotatable structures to sequentially addressindependent sample arms and permit the collection of low coherencesource light backscattered from several different samples or fromseveral locations on a single sample utilizing a single sweep of one ormore adjustable delays. The interference signals from the deviceprovides information on areas or regions of the sample, and can be usedto discriminate between health and diseased tissue.

Versions of the invention include sensing devices that areinterferometers and or autocorrelators. The interferometers includemultiple sensing arms and one or more reference arms, theautocorrelators include multiple probe arms and an interferometer ordelay compensator. The devices use one or more broadband light sourcesand waveguides configured to enable the collection of low-coherenceinterferometric (LCI) signals from several samples or several locationsof a sample, all in a single trace. The interferometers andautocorrelators include two or more waveguides that collect lowcoherence source light backscattered from a sample. The backscatteredlight is from the sample is combined with reference light to produce alow-coherence interferometric signal that is detected by a detector. Bysweeping a variable delay of the device, for example an optical delay ofa reference arm or delay compensator, interferometric signalscorresponding to each of the waveguides collecting the backscatteredlight from the sample are produced. The low coherence interferometricsignals from sensor provide information about the morphology, physicalnature, composition, and properties of the of the sample it is inproximity with. The sensor may be used to discriminate between finishedsurfaces and corroded surfaces, healthy and diseased tissue, and cansample the material or tissue in two or more areas. In applicationsrequiring the collection of several LCI traces in a short time, thecollection of information from several locations in a single traceconsiderably reduce the time for data collection.

Reference arms refer to structures that include waveguides, opticalfibers, free space structures, or a combination of these along with oneor more reflectors that produce reference light from the low coherencesource light that is within the coherence length of the lightbackscattered from the sample. Examples of reference arms include (422)in FIG. 4, (1310) and (1314) in FIG. 13, and can include an arm in theinterferometer section of the autocorrelator, for example (746) in FIG.7. A delay compensator is an interferometer structure that can includewaveguides, optical fibers and reflectors that compensate for theseparation of the reference and backscattered light from a sample thatis outside the coherence length of the source.

Sample arms can be waveguides, optical fibers, free space structures, ora combination of these that propagate low coherence source light to asample and collect backscattered source light from the sample. Probearms refer to a type of sample arm where the waveguide reflects aportion of the source light to provide reference light, propagate sourcelight to the sample, and collect backscattered light from the sample.The probe arms propagate both reference and backscattered light. Probearms include a partial reflector at a short distance from the tip of theprobe. The light reflected from the partial mirror is used as thereference light. The value of the reflection coefficient of the partialreflector determines the amount of the reference light and can be lessthan 100% percent, is preferably from about 30-36% and is mostpreferably between 32 and 34%. The sensing arm, which collects thebackscattered light, for example the interferometric sensor, may containan optional modulator whose frequency can be detected by the receiverfor amplification and processing.

Adjustable or variable delays can be used in the sample arms, probearms, reference arms, and delay compensator arms to modify the opticalpath of light propagating in the arms. The delay can be a time delay, achange in the optical pathlength of the arm, or a change in the index ofrefraction of a portion of the arm.

Low coherent light or activating light in the sensor devices can bepropagated in waveguides, optical fibers, wavelength divisionmultiplexers, Faraday rotators, and in free space. Various structuresincluding but not limited to splitters, couplers, and circulators can beused to couple the propagating light into various structures of thesensor device.

A processor can provide an output, for example but not limited to adigital, current, voltage or combination of these, that is proportionalto the interference measured and includes phase, amplitude, or acombinations these between the sample and reference light propagated bywaveguide elements of the sensor. When multiple wavelength sources areused to probe a sample simultaneously, an array of photodetectors can beused, one for each wavelength, with a light dispersion element to directthe correct wavelength light to the photodetectors. Alternatively, oneor more additional delays can be introduced to separate the variousLCI's so that a single detector may be used.

FIG. 1 illustrates the operation of an ordinary single-arm low-coherenceMichelson interferometer using single-mode or polarization-maintainingoptical fibers. FIG. 1 shows an all-fiber low-coherence interferometer.It consists of a broad-band light source (110), such as asuperluminescent diode (SLD), an optional isolator (106) coupled to afiber (114), a fiber splitter (118) (a useful ratio for the splitter is50:50), an optical detector (122), and two arms: one arm, is referred toas the reference arm (126), that has adjustable length L using piezostretcher (142) with a mirror (130) at its end and carries the referencelight E_(r); the other arm, is referred to as the sensing arm (134),allows light to penetrate to a distance (z) in a medium, object, orsample (138), and captures the reflected or back-scattered light E_(s)from the sample (138). The length L in the reference arm corresponds atime delay τ undergone by E_(r). Different path lengths for lightinteracting with the sample may be probed by the interferometric sensorthrough adjustment of the physical length, optical length, or opticaldelay of the reference arm of the interferometer. Interference betweenthe reference arm and sample arm light occurs when the optical pathlength between the two is within the coherence length of the sourcelight. This length or delay can be provided by either moving the mirror(130) at the end of the reference arm, or by providing a device tostretch the fiber. This stretching can be achieved by winding part ofthe fiber around a piezoelectric (PZT) drum (142) to which a voltage isapplied. The PZT stretcher (142) has the advantage of using nomechanical moving parts, and therefore can be relatively fast. Byapplying a voltage ramp to the PZT (142), the length can be changed orscanned over a given range to provide path length matching with thelight from within the sample under study. For scanning over broadranges, mechanical scan with the moving mirror (130) can be used. Forbiological tissues, which are highly scattering, the maximum depthz_(max) for penetration of light in the sample is of the order of 1-2millimeters (mm), and the PZT scan can be used. A 15-meter length offiber wound around a PZT drum can provide a length, nL, of 5-10 mm,where n is the effective refractive index of the fiber, with theapplication of a peak voltage of about 500 volts in a 50-millisecondramp. Several other configurations can be adopted to describe theinterferometer. A similar but shorter delay length L₁ or time delay τ₁can be applied to the sensing arm, by the modulator (146).

In operation, light, electric field E_(r), reflected from the referencemirror (130) and the light, electric field E_(s), reflected or scatteredfrom depth z within the object or sample(138) under study are combinedat the detector (122), whose output current, I_(D) is proportional tothe squared magnitude E_(i)E_(i)* of the total electric field E_(i),which is the sum of E_(r) and E_(s), which is time-averaged andintegrated over all frequency components of the light source.

If the power density spectrum of the light source is S(ν), then thedetector current is given by, (assuming a conversion efficiency of 1ampere per watt):

$\begin{matrix}\begin{matrix}{I_{d} = {\int_{0}^{\infty}{{S(v)}\left( {E_{r} + E_{s}} \right)\left( {E_{r} + E_{s}} \right)^{*}\;{\mathbb{d}v}}}} \\{= {{\int_{0}^{\infty}{{S(v)}\left( {{E_{r}E_{r}^{*}} + {E_{s}E_{s}^{*}}} \right)\;{\mathbb{d}v}}} +}} \\{2\;{Re}\left\{ {\int_{0}^{\infty}{{S(v)}\;{E_{r}\left( {t + {\Delta\;\tau}} \right)}\;{E_{s}^{*}(t)}\;{\mathbb{d}v}}} \right\}}\end{matrix} & (1)\end{matrix}$

where the star (*) represents the complex conjugate of the total field,and Δτ is the relative time delay between the reference and signal lightbeams, given by

${\Delta\;\tau} = \frac{{n\; L} - {n\; L_{1}} - {n_{s}z}}{c}$

where n is the fiber refractive index and n_(s) is the refractive indexof the object under test.

If the source spectrum is Gaussian, then

$\begin{matrix}{{{S(v)} = {\frac{p}{\sqrt{\pi}}\;{\exp\left\lbrack {- {p^{2}\left( {v - v_{0}} \right)}^{2}} \right\rbrack}}},{{{where}\mspace{14mu} p} = \frac{2\sqrt{\ln\; 2}}{\Delta\; v}}} & (3)\end{matrix}$

where ν_(o) is the center frequency and Δν is thefull-width-half-maximum (FWHM) frequency bandwidth of the source. Theintegrals containing E_(r)E_(r)* and E_(s)E_(s)* yield constantquantities, representing DC currents I_(r) and I_(s) from the referenceand signal lights alone, and contain no information. The term involvingthe product E_(r)E_(s)* is the interference signal containinginformation about the object.

It is convenient to represent the interference signal in terms of theeasily measurable center wavelength λ_(o), the FWHM wavelength bandwidthΔλ of the source, and in terms of the distances L, L₁, and z. After somemanipulation, the following relationship can be obtained, using νλ=c,where c is the speed of light in vacuum, and using Δν=cΔλ/λ²,

$\begin{matrix}{{i_{s}(z)} = {2\;{Re}\left\{ {\int_{0}^{\infty}{{S(v)}\;{E_{r}\left( {t + {\Delta\;\tau}} \right)}\;{E_{s}^{*}(t)}\;{\mathbb{d}v}}} \right\}}} & (4) \\{\mspace{45mu}{= {\sqrt{I_{r}{I_{s}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{1}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{1}}{\lambda_{o}} \right)}}}} & \; \\{where} & \; \\{{\Delta_{1} = {{n\; L} - \left( {{n\; L_{1}} + {n_{s}z}} \right)}},{and}} & (5) \\{L_{c} = {\frac{2\sqrt{\ln\; 2}}{\pi}\frac{\lambda_{o}^{2}}{\Delta\;\lambda}}} & \; \\{\mspace{25mu}{\approx {0.44\;\frac{\lambda_{o}^{2}}{\Delta\;\lambda}}}} & \;\end{matrix}$

where L is the variable component of the reference arm, L₁ is theoptional delay added to the sensing arm, and where L_(c) is theso-called coherence length of the source.

Since I_(r)=E_(r)E_(r)*=|E_(r)|², then E_(r)=√{square root over(I_(r))}. Similarly, E_(s)*=√{square root over (I_(s))}. Moreover, I_(s)is a function of its starting depth z in the sample and of itsreflection and scattering properties. In particular, if the sample is ascattering material, theory shows that E_(s) has a complicated andexponential dependence on z. This is illustrated in FIG. 2 for a skinsample and I_(s)(z) can be expressed as a function of z. This type ofprofile is predicted by scattering theory in general. The specificprofile depends on the type of medium, material, or tissue beingexamined. One of the main features of LCI, as applied to scatteringtissues, is to experimentally obtain this profile for arbitrary tissues,whether the tissue is the dermis, as for determining features such asglucose concentration, or arterial walls as for the detection ofvulnerable plaques. It is expected that deviations in the composition ofa surface, for example due to corrosion, or health of a tissue due tonecrosis or presence of a tumor will result in features that aredetectable compared to normal surfaces (no corrosion or healthlytissue).

The exponential function in Eq. (4) can be referred to as G(Δ₁), i.e.,

$\begin{matrix}\begin{matrix}{{G\left( \Delta_{1} \right)} = {\exp\left\lbrack {- \left( \frac{\Delta_{1}}{L_{c}} \right)^{2}} \right\rbrack}} \\{\mspace{59mu}{= {\exp\left\{ {- \left\lbrack \frac{{n\; L} - \left( {{n\; L_{1}} + {n_{s}z}} \right)}{L_{c}} \right\rbrack^{2}} \right\}}}}\end{matrix} & (6)\end{matrix}$

In practice L can be made to vary discretely or continuously from 0,even a negative value, or some chosen maximum value and that Δ₁ willvary accordingly. In particular, Δ₁ value is zero when nL=nL₁+n_(s)z,i.e., when the reference arm length matches the probe arm length foreach value of z. The coherence length L_(c) is a function of thesource's center wavelength λ_(o) and FWHM bandwidth Δλ. For example, asource with 1310 nm center wavelength and 50 nm bandwidth, the coherencelength is 15 microns. As shown in FIG. 3 a, G(Δ₁) is unity for Δ₁=0; itfalls off to 0.37 for Δ₁=±L_(c) and then rapidly to zero for Δ₁>L_(c).

The cosine term in Eq. (4), cos(2πΔ₁/λ_(o)), is the real interference,and the argument of the cosine is its phase. It undergoes maxima andminima every time Δ₁ changes by λ_(o)/2, with period λ₀. This is anextremely sensitive function of position and of the refractive indexn_(s) of the sample at position ζ. The product G(Δ₁)cos(2πΔ₁/λ_(o)) isplotted in FIG. 3( b). It shows G(Δ₁) as an envelope which acts as agate or window which limits the measurable interference signal to anarrow depth of width 2L_(c) and centered at the depth location z whichgives Δ₁=0 in the neighborhood of the depth z. Since I_(r) is a constantand I_(s)(z) is a function of z, the LCI signal thus is a probing orsampling of the magnitude of the light reflected or scattered from depthz within a resolution of ±L_(c).

For a given depth z for which Δ₁ is zero, the interferometric signal isgiven by its peak value which, from equation (4) isi _(s)(z)={square root over (I _(r) I _(s))(z))}{square root over (I_(r) I _(s))(z))}   (7)

Thus by ramping L, for example at a constant rate ν such that L=νt,where t is the time, and continuously measuring the peak of the detectedsignal, then the plot of Equation (7) vs. L can be used to plot I_(s)(z)in a manner similar to FIG. 2 for the sample under test over the fullmeasurable depth z_(max). This can be computed by the processor section(150) illustrated in FIG. 1 connected to the detector.

In a typical LCI or OCT (optical coherence tomography) system, only themagnitude of the interference is measured, and the process isessentially as described above. More sophisticated systems can bedesigned to measure both the magnitude and the phase of the signalinterference signal. Such systems are described in detail in PatentApplications invented by Gerard A. Alphonse and assigned to MedeikonCorporation Exp. Mail No. EL 732725416 US, titled LOW COHERENCEINTERFEROMETRY UTILIZING MAGNITUDE, and Exp. Mail No. EL 732725393 US,titled LOW COHERENCE INTERFEROMETRY UTILIZING PHASE the contents of eachbeing incorporated by reference in the present application in theirentirety. Although the remainder of the present application will bedescribed with reference to amplitude measurements of interference, theclaims are not limited to amplitude measurements of interference and mayinclude phase measurements and combinations of these where applicable.

The sensors in various embodiments of the present invention are devicesthat can have two or more sensing arms and one or more reference arms.The plurality of sensing arms in an interferometer or plurality ofcombined reference and sensing arms in an autocorrelator can beconfigured to acquire low coherence interferometric information on asample(s) from all the arms in a single trace during a sweep of avariable delay of one or more reference arms or a delay compensator.Through use of appropriate delays in the sample arms, for example a timedelay, refractive index change, a change in length of a waveguide, orany combination of these in any of the sample arms, the individual lowcoherence interferometric signals from each of the sample arms may beresolved or separated.

In many sensing and diagnostic applications the collection of severalLCI signals in a short time either from a single sample region or fromseveral regions or directions along a sample is beneficial in terms ofreduced examination time and reduced costs. Further, the configurationof the sample arms and reference arms in the present inventioneliminates the complexity and costs associated with use of an externaloptical switches or multiple interferometers, even those formed on asingle substrate, to simultaneously probe different areas of a sample.

The optical sensor device in embodiments of the present invention mayconsist of elements from a free space device, fiber optic elements,integrated optics, or a combination of these. While free space deviceconfigurations are possible, waveguides, such as but not limited tomonolithically formed channel guides or optical fibers are preferred inthe present invention. Through the use of multiple waveguides for samplearms to propagate low-coherence light and to collect backscattered lightfrom the sample, information about the sample may be obtained in asingle sweep of the variable delay of a reference arm or delaycompensator. This obviates the need and limitations of birefringentcrystals or optical switches to address multiple sample arms. The use ofwaveguides provides greater latitude in the size, shape, and flexibilityin the design and use of borescopes, endoscopes, and catheters forprobing a wide variety of cavities, vasculatures, and conduits.

Light sources useful in the present invention can include those whichare capable of penetrating material samples and providing torturous aswell as ballistic light trajectories in the sample. Examples of suchlight sources include low coherence light sources or multiple lowcoherence light sources with different center wavelengths whose outputshave been combined. The source may emit in the near infrared andinfrared, have a short coherence length, and have high irradiance forpenetrating deep into the sample. Preferably for probing tissue, the lowcoherence light sources have wavelengths in a range of from about 600 toabout 1800 nm. Examples of sources include but are not limited to edgeemitting LEDs, superluminescent diodes, and multiple quantum well lightemitting diodes. One or more light sources having the same or adifferent wavelength may be used or one or more multiple quantum welldevices may be formed on a single substrate to provide multiplewavelengths. The penetration of light into a material sample, preferablya tissue sample can vary with the wavelength and power of the of sourcelight used, use of optical circulators, coupling losses and componentattenuation of light, and the type of material being scanned. As anillustrative example for the sensor depicted in FIG. 15, low coherencelight sources (1510), (1512), (1514) and others (not shown) each havinga different center wavelengths can be coupled before the circulator(1530) through a wavelength division multiplexer (1522) (WDM). In usethe sample (1554) may be illuminated by a low coherence light sourcewith a center wavelength of for example 800 nm, 1300 nm, or 1800 nm. Byusing more than one wavelength of low coherence source light to probethe sample, the sample can be probed at different depths andspectroscopic information about the sample can be obtained during atrace.

The profile of the light beam profile outside of a waveguide or fibercan be modified to maximize backscattered light collected by thewaveguide. Collimating the beam can be used to achieve this for exampleby use of a GRIN lens, the use separate microlens fixed to the end ofthe waveguide or fiber, a collimating structure fabricated on theoutside of the glass wall such as those as illustrated by structures(1610) and (1650) in FIG. 16, or laser micromaching the tip of thefiber. FIG. 16( a) illustrates a probe for an interferometer that has ahousing (1604) enclosing two or more sample arms (1614), (1618), andothers not shown. The sample arm waveguides (1614) and (1618) propagatelight to the reflecting prism (1606) where it is directed radially outthrough a collimator sleeve (1610) mounted to the housing (1604). Sourcelight and backscattered light (1608) from a sample that is propagated bywaveguide (1614) passes through the collimator (1610) while source lightand backscattered light (1628) from a sample that is propagated bywaveguide (1618) also passes through the collimator (1610). FIG. 16( b)illustrates a probe arm that has a housing (1664) and waveguides (1632)and (1652) each having partial reflectors (1656) and (1634) respectivelyand delay elements (1638) and (1642) respectively. Source light andbackscattered light (1648) from a sample that is propagated by waveguide(1632) passes through the collimator (1650) and source light andbackscattered light (1668) from a sample that is propagated by waveguide(1652) passes through the collimator (1650). An optional spacer (1612)or (1644) may be included in the housing to maintain the spacing of thefibers within the housing.

FIG. 4 shows an embodiment of multiple probes based on a Michelsoninterferometer having multiple sensor arms (410) and (414) and others(418) and a single reference arm (422). In this configuration, thesingle sensing arm of the standard interferometer is replaced by amultiplicity of sensing arms joined together by means of a 1:N coupler(426) such as a commercially available star or tree coupler. This treecoupler (426) preferably splits its input light equally among the Nbranches. The preferred splitting ratio at the main splitter (430)dividing light between the reference and sample sections is about 50:50(50% for the reference arm and 50% for the tree coupler).

In FIG. 4, the different branches are shown to probe the same generalarea of a sample (438). Without limitation the sample arm branches canbe oriented in different directions on the sample, the branches may bein contact with different samples, or the branches may be in contactwith a sample and a reference material. The operation of the system canbe analyzed in the same manner as the ordinary interferometer, with theinput electric field to the detector being the sum of the electricfields returning from the reference arm (422) and all the sensing arms(410), (414), and others (418). The analysis of the interferometer, videinfra, is shown for two sensing arms, but the results can be extended toan arbitrary number of sensing arms. In the case of two sensing arms(410) and (414), the total electric field E_(i) at the detector (442) isthe sum of the reference field E_(r) and those of the two sensing armsE_(s1) and E_(s2). The resulting detector current may be given by Eq. 8:

$\begin{matrix}{I_{d} = {\int_{0}^{\infty}{{S(v)}\left( {E_{r} + E_{s1} + E_{s2}} \right)\left( {E_{r} + E_{s1} + E_{s2}} \right)^{*}{\mathbb{d}v}}}} & (8)\end{matrix}$from which the interferometric signal is found to be a single tracehaving the two components

$\begin{matrix}{{i_{s}(z)} = {{i_{s1}(z)} + {i_{s2}(z)}}} & (9) \\{\mspace{40mu}{= {{\sqrt{I_{r}{I_{s1}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{1}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{1}}{\lambda_{o}} \right)}} + {\sqrt{I_{r}{I_{s2}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{2}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{2}}{\lambda_{o}} \right)}}}}} & \; \\{{{{where}\mspace{14mu}\Delta_{1}} = {{n\; L} - \left( {{n\; L_{1}} + {n_{s}z}} \right)}},{{{and}\mspace{14mu}\Delta_{2}} = {{n\; L} - \left( {{n\; L_{2}} + {n_{s}z}} \right)}}} & (10)\end{matrix}$

An important aspect of this invention is the ability to independentlyretrieve these two components, in other words to completely or partiallyprevent them from overlapping in the LCI trace. The key lies in thechoice of the total scanning distance L, of the reference arm (422), theindividual sensing arm distances L₁ and L₂, and the gating property ofthe functions G(Δ₁) and G(Δ₂) shown below

$\begin{matrix}\begin{matrix}{{G\left( \Delta_{1} \right)} = {\exp\left\lbrack {- \left( \frac{\Delta_{1}}{L_{c}} \right)^{2}} \right\rbrack}} & {and} & {{G\left( \Delta_{2} \right)} = {\exp\left\lbrack {- \left( \frac{\Delta_{2}}{L_{c}} \right)^{2}} \right\rbrack}}\end{matrix} & (11)\end{matrix}$

FIG. 5 illustrates how two LCI profiles from separate sample arms can beresolved with a single trace of the reference arm (422). This can beachieved, for example, by allowing the instrument shown in FIG. 4 toscan the reference arm (422) length L at speed v over a time duration t,with the sample arms configured so that L₂>L₁+z_(max) and L>L₂+z_(max).In this configuration independent observe or measure the back-scatteredLCI profiles I_(s1)(z) and I_(s2)(Z) can be made. FIG. 5 shows theappropriate relationship among L₁, L₂, z_(max), and L to achievecomplete resolution of profiles I_(s1)(z) and I_(s2)(z). If L₂=L₁, thenthe two signals will occupy the same space in the trace. However, ifL₂>L₁+z_(max), then I_(s2)(z) will be separated from I_(s1)(z) by adistance equal to n₂L₂−n₁L₁ where n₂ and n₁ are the refractive indicesof the sample arms. When L>L₂+z_(max), then both LCIs will be fullyseparated and complete, as illustrated in FIG. 5. The configuration andassembly of a sensor with more than two probes where the low coherenceinterferometric signals from at least two of the sample arms ispartially resolved, preferably where the low coherence interferometricsignals from all of the sample arms are completely resolved, can be madeusing these criteria.

In various configuration of the devices in the invention, for examplethose utilizing two or more sample arms coupled to one or more referencearms, or two or more probe arms coupled to a delay compensator, it ispossible to use materials with different indices of refraction, mirrors,or fiber stretching to modify an adjustable delay resulting in partialor complete resolution of the individual LCI signals from thebackscattered sample light collected by the sample arms. Complete LCIsignal resolution may be achieved, partial resolution of LCI signalsfrom one or more of the sensing arms may be achieved, or a combinationof these may be achieved. Resolution refers to the process or capabilityof making distinguishable at least some of the individual parts of theinterference signal from two or more sample or probe arms producedduring a single sweep of the adjustable delay of the reference sectionor delay compensator respectively. Where partial resolution is achieved,adjustments, including but not limited to the size of L, L_(m), (where mis an integer describing the number of sample or probe arms in thesensor), the index of refraction n of the sample, probe delayadjustment, delay compensator arms adjustment, adjustment of one or morereference arm(s), or adjustment of the depth of penetration of light inthe sample z can be used to modify the degree of separation achievedbetween multiple LCI signals.

One version of the invention is an interferometric sensor including twoor more sensing arms each having an adjustable delay (416) and (420),and a reference arm also having an adjustable delay (412) as shown inFIG. 4. The sensing arms and reference arms can be coupled (430) to oneor more low coherence light sources (404) and utilize an optionalisolator (408). The reference and sample arms of the sensor may beconfigured, for example by a change in their length, a delay time,position of moveable mirror (434), or a change in the index ofrefraction of the guide so that the delay for each of the sample armsand reference arm is within the coherence length of the source light.Backscattered sample light from the two or more sensing arms and thereference arm light are coupled together and interference measured bydetector (442). A signal proportional to the interference measured foreach of the sample arms during a sweep of the delay (412) can bedisplayed, compared to normal material, or digitized using processor(450).

Various devices of the present invention may include light sources,detectors, and processor, or components of these devices may beconnected to pre-existing light sources, detectors and other componentsusing waveguides and electrical connectors. For example, theinterferometric sensor of FIG. 4 may include a low-coherence lightsource. Alternatively, splitter (430) can be coupled to one or morepre-existing low-coherence light sources available in a hospital orlaboratory. The interferometric sensor described can be coupled to aseparate or existing detector using waveguide (446), or it may include adedicated detector (442) to measure the intensity of interferencebetween the reference and light backscattered from the sample. Thedetector may further be connected to an existing processor, or adedicated processor (450) as shown in FIG. 4, that can provide anoutput, for example but not limited to a digital output, a currentoutput, or a voltage output that is proportional to the interferencebetween the backscattered light and reference arm (or delay compensatoradjusted) light measured by the detector for each sensing arm.Preferably adjustment of the reference arm adjustable delay or the delaycompensator adjustable delay is capable of resolving backscattered lightinformation from at least two sample or probe arms. The adjustable delayin the delay compensator arms, reference arms, or sample arms can bevoltage actuated, current actuated, digitally actuated, or actuated byacombination of these. The sensor devices preferably includes sample,delay compensator, and reference arms which are made from fiber orsingle-mode waveguides and preferable uses polarization-maintainingwaveguides.

LCI autocorrelators can also be configured to have multiple sample orprobe arms. One of the advantages of the autocorrelator is that they canbe built from single-mode fibers, which is less expensive and lesscomplicated to use than polarization-maintaining fibers. FIG. 6 shows anexample of an autocorrelator. It consists of an interferometer and anindependent probe (610) which carries both the reference light and thesensing light. A portion of the source light (618) is partiallyreflected light from the partial reflector (614) near the tip of theprobe (610) to form reference light E_(r). The sensing light is thelight transmitted into the sample (638) and back-scattered andpropagated by fiber (610). Thus, there is a distinct delay between thereference and sensing light, the delay being twice the distance thelight travels beyond the fiber tip and into the sample. This distance ismuch longer than the coherence length of the source (618), and thereforethe reference and object light cannot interfere with each other. Thepath length correction for interference can be provided by theinterferometer. The probe (610) is connected to the broadband source(618) (the isolator (620) is optional) by means of a circulator (622). Acirculator (622) is a three-port device in which light injected at oneport is transmitted to a second port, but the light reflected from thesecond port is deflected to a third port; a splitter can also be used,but the isolator is more efficient. The electric field of the referencelight can be designated as E_(r), starting from the value E_(or) at thereflector. The field from the sensing light may be designated as E_(s),and its initial value is E_(os). A short length L₁ of fiber (624),terminated preferably with an antireflection coating, can be used toprovide a controlled delay τ₁.

An advantage of having the reference and sensing lights in the samefiber when using single-mode fiber is the fact that the relativepolarization between the two lights is maintained under anycircumstance. This is important because interference occurs between thelight beams when they have the same polarization. In the event the extrawaveguide length L₁ is used, it is preferable for it to be a section ofpolarization-maintaining fiber, or any material that minimizes loss ofpolarization, in order to avoid any loss of polarization in short lengthL₁ of fiber (624). This arrangement is easily achieved, for example butnot limited to deposition of a partial mirror at the end of the mainfiber (614), then fusion of the element with delay L₁ (624) piece to thepartial mirror.

The total electric field in the probe, which is the sum of E_(r) andE_(s) is directed to the interferometer from the third port (628) of thecirculator (622). This light serves as the input to the interferometeror delay compensator section of the device.

The delay compensator consists of two similar arms (632) and (634) thatcan be made to have identical or nearly identical lengths or delays withtwo devices (642) and (646), that can be but are not limited to a PZTfiber stretcher. The devices (642) and (646) are also capable ofproviding a variable relative delay between the delay compensator arms(632) and (634). The delay can be obtained by a mechanical device, forexample a voltage, current, or digitally actuated moving reflector. Apreferred device can include winding a length of the fiber (632) and(634) in each arm around separate PZT drums and applying a voltage tothe PZT drums. The application of a voltage of one polarity expands thePZT drum, hence stresses the fiber to increase its length by the amountL and provide a delay τ. Applying a voltage of the reverse polarity willhave the opposite effect. By applying a voltage of one polarity to onedrum (642) and of the opposite polarity to the other drum (646), a roundtrip effective path difference of 4L or a delay of 4τ can be achieved.As an example, a 15-meter length of fiber wound around a PZT drum canprovide a length nL of 5-10 mm, with the application of a peak voltageof about 500 volts in a 50-millisecond ramp. To preserve thepolarization relationship of light in the two reference arms (632) and(634), especially upon reflection, Faraday rotator reflectors (650) and(654) can be used in the interferometer.

In operation, the delay compensator input light E_(i)=E_(r)+E_(s) iscoupled to the delay compensator and is split by the splitter (658) intotwo equal components which, upon reflection from the Faraday mirrors(650) and (654), becomes E_(C) and E_(D), with their respective delays,so that the total light input to the detector is E_(T)=E_(C)+E_(D). Themathematical analysis of this system shows DC terms, someinterferometric terms with delays that are always much larger than L_(c)(the coherence length) and therefore are vanishing, and two terms whichcombine to give the current i_(s)(z)

$\begin{matrix}{{i_{s}(z)} = {\left( {1 - R} \right)\sqrt{R}\sqrt{I_{r}{I_{s}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta}{\lambda_{o}} \right)}}} & (12)\end{matrix}$where R is the power reflection coefficient at the probe tip, and whereΔ=4nL−2(nL ₁ +n _(s) z)  (13)

By applying a voltage of one polarity to one drum (642) and of theopposite polarity to the other drum (646), a round trip effective pathdifference of 4L or a delay of 4τ can be achieved. Without limitation,other path length differences may be achieved in the delay compensatorby applying different voltages to the drums so that the difference inEq. 13 is within the coherence length of the source light andinterference occurs.

This result is similar to the ordinary Michelson interferometer exceptfor the fact that Δ is double the difference between the scan length andthe path length between the reference and sensing lights. The commonpath between the reference and signal cancels out. Thus, although thepath difference between the reference and sensing lights in the probearm (610) is much larger than the coherence length, the delaycompensator path difference can bring it under the coherence gatingfunction. In particular, the detector (662) can measure the peak of thesignal corresponding to any depth z with the sample is obtained when 2nL=nL₁+n_(s)z.

One version of the invention is a sensor that includes two or more probearms that are capable injecting source light into a sample andcollecting backscattered light from the sample and capable or producingreference light. The probe arms are coupled to a tree splitter which isitself coupled to a low-coherence light source through a circulator orsplitter. Each probe is configured so that it propagates reference lightand also propagates light backscattered from the sample. This is done byinserting a partial reflector at a short distance from the tip of theprobe. The light reflected from the partial mirror can be used as thereference light. The value of the reflection coefficient of the partialreflector determines the amount of the reference light. The light thatis transmitted through the section of the waveguide beyond the partialreflector is used as the probing light itself, and this section ofwaveguide is used to transmit the probe light to the sample and collectthe backscattered light from it. This backscattered light is thencoupled to the main section of the probe through the partial reflector.In this manner, the probe contains both the reference light and thebackscattered light. The short distance between the partial reflectorand the tip of the waveguide provides a well defined delay between thereference light and the backscattered light. In a multiple probe arminstrument, each arm would have an appropriate length determined by theamount of separation desired among the signals from the individual arms,and the various arms are joined together using a tree coupler. The 1×Ntree coupler is an optical component that enables light to be coupledfrom one waveguide to N waveguides and vice-versa. In various versionsof the invention, the tree coupler is used to split the light from abroadband light source equally among the N branches. In the case of adevice using probe arms, the tree coupler splits light from thebroadband source among the N branches and then combine the lightbackscattered from the sample (the reference lights and thebackscattered lights) back into that single waveguide. Light from abroadband source can be coupled to the multiple-arm probe by usinganother coupler, which is preferably a circulator. The circulatorprevents the reflected light from affecting the broadband light source.In this version of the invention, the sensor also includes a delaycompensator or delay equalizer, which is connected to the third port ofthe circulator such that the total reflected light in the multiple-probearms from the sample is fed to the delay compensator. The delaycompensator is an interferometer which consists of two delay arms withadjustable delays between them, and reflectors at the end of each arm.In order to maintain polarization, particularly if the delay arms aremade from single-mode fibers (as opposed to polarization-maintainingfibers), Faraday rotator reflectors are used. A Faraday reflectorconsists of a Faraday rotator and a mirror. The light entering a fiberfrom a Faraday reflector is such that its polarization is exactly thesame as that of the light entering the Faraday reflector from the fiber.The purpose of the adjustable delays is to compensate for the fact thatthe respective delay between the reference and backscattered light inany individual probe arms is normally significantly larger than thecoherence length, and therefore cannot interfere together by themselves.The compensator delay compensates for that delay and brings theinterference between these two lights to within the coherence length ofthe light source by compensating for the original delay between them.

The adjustable delay can be obtained in several ways. One way is to makethe position of the mirror of the Faraday rotators individuallyvariable. Another way is to make the length of the two arms of equal ordifferent lengths and including a fiber stretcher in each arm forproviding the delay or for fine-tuning of the delay. The delay arms ofthe interferometer component connected to the third port of thecirculator are configured such that all the interferences between thereference and backscattered light from all the probes occurssequentially under a single trace of the delay compensator arms throughtheir adjustable delay. The various interference signals appear withinthe gating windows determined by the coherence length of the lightsource. The interference signals are measured by a detector that can becoupled to one of the return leads of the splitter in the interferometersection.

The sensor devices can include one or more a low-coherence light sourceincluding an activation light source for photodynamic therapy, orsubcomponents of the sensor device, for example it may be connected toan existing low-coherence light source. A detector, which may be aseparate existing detector or a dedicated detector, can be coupled tothe circulator, and the delay compensator arms. The detector measuresthe interference between the light reflected from the partial reflectorsand backscattered light from the sample that is collected by theindividual probe arms. The detector may further be connected to aprocessor that provides an output proportional to the interferencesignals. In this version of the sensor, the probe is preferablyconfigured so that interference between reflected source light andbackscattered source light from the sample does not occur directly, butrather as a result of the compensation delay in the interferometer ordelay compensator section. Preferably the polarization of light in boththe probe and delay arms is maintained, even more preferably Faradaymirrors are used as reflectors in the delay compensator arms,interferometric arms, of the sensor. The adjustable delay in the probesor delay arms may be electrically or digitally actuated to achieve thedesired delay between the interferometer arms, length matching ormodulation of the reference section of the probe arms. Where the lengthof the probe arms are adjusted, preferably the length of waveguidebetween the sample and the partial reflector is not equal for two ormore probes.

An autocorrelator with multiple probes is shown in FIG. 7. Instead ofthe single probe of the ordinary autocorrelator illustrated in FIG. 6,the autocorrelator now has a multiple probe branches or sample arms(708), (710), and other probe branches or sample arms (712) coupled to astar or tree coupler (704) that is itself coupled, or capable of beingcoupled, to a circulator (722) with output ports (706) and (728). Eachprobe branch consists of a common path waveguide for the reference andbackscattered sample light, the waveguide may be an optical fiber or amonolithically formed waveguide on a substrate. Light from one or morelow coherence sources (718) through optional isolator (720) ispropagated to the sample (738) through port (706) of the circulator(722), through tree coupler (704) coupled to the multiple probe arms(708), (710), and other probe arms (712). The waveguide for each probebranch has a partial reflector near the end of the waveguide, such as(714), (716), and partial reflectors not show for the other branches(712), and a unique delay element, such as ((724) with delay L₁, τ₁))and ((726) with delay L₂, τ₂), and delay elements not shown for theother branches with delays L_(m), τ_(m)) where m is an integerrepresenting the other branches present. The length of the delayelements are chosen so that the path difference between the referencelight and sensing light is larger than the coherence length of thesource. The delay elements may be fused to the partial mirror depositedon the end of the waveguide or fiber. The delays would be located afterthe partial reflector along the waveguide. The delay elements, such as(724) and (726), can be designated by the lengths L₁, L₂, up to L_(m),or the time delays t₁, t₂, up to t_(m). Optionally, it is also possibleto add to each arm the small delays such as length adjust elements,(730) and (734), which can be small PZT drums on which are wound thesmall fiber sections to provide the length-adjust elements δ₁, δ₂, . . .δ_(m) and d₁, d₂, . . . d_(m).

FIG. 7 also illustrates the three sections for an autocorrelator versionof the present invention that includes a probe section (702), delaycompensator section (740), and signal processing section (760). Themultiple probes (708), (710), and (712) carry both reference andbackscattering signals and along with the optional adjustable delay(s)((730), δ₁ and d₁) and ((734), δ₂ and d₂) that make up the probesection. The delay compensator section includes the waveguides (742) and(746) with variable delays ((744), L and τ) and ((748), L and −τ) andFaraday reflectors (750) and (754) and is used to compensate for orequalize the path differences between the reference and backscatteredlights in the individual probe branches. The detector or signalprocessing section (760) includes the detector (766) and processor (768)that are coupled or capable of being coupled by waveguides (770) and(774) to the circulator (722) and interferometer delay compensatorsection through splitter (758).

The electric field in each branch of the multiprobe is the sumE_(rk)+E_(sk) of the reference field E_(rk) and signal field E_(sk) inthat branch, where k is an integer (k=1, 2, 3, . . . up to number ofprobes). These fields are summed together in the tree coupler (704) andfed to the interferometer or delay compensator through the output port(728) of the circulator (722). All the electric field elements willinteract and interfere at the detector (766) after passage through theinterferometer, but that only those interactions which, together withthe interferometer delay, can exhibit a path difference shorter than thecoherence length will produce a useful LCI signal. In particular, it isexpected that the field from each signal branch can interfere not onlywith its own reference field (self-referenced), but also with thereference fields from all the other branches to produce additional LCIsignals for that particular branch (cross-referenced). The presence ofcrossed-referenced signal components can be used to provide automaticaveraging or summing of an LCI without the need for repeated scanning.

The multiple combined reference and sensing probe arms of anautocorrelator can be used to produce LCI signals from all the samplearms during a single sweep of one or more variable delays of the delaycompensator. The probe arm also has a variable delay, for examplevariable length L_(m) or time τ_(m). By applying appropriate delays tothe delay compensator, it is possible to produce LCI signals for each ofthe probe arms by virtue of the gating property of the exponentialfunction G(Δ).

For an autocorrelator having multiple probe branches or sample arm, thetotal backscattered interferometric signal may be described by thebackscattered light propagated by each of the branches as well as crossterms related to the combination of the reference light from thebranches. For two probe branches, the LCI signal can be described by thefollowing expression containing the following four terms:i _(s)(z)=i _(s11)(z)+i _(s12)(z)+i _(s21)(z)+i _(s22)(z)  (14)

where assuming, for simplicity, that the power reflection coefficientfor the reference light at each branch has the same value R:

$\begin{matrix}{{{i_{s11}(z)} = {\left( {1 - R} \right)\sqrt{R}\sqrt{I_{r1}{I_{s1}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{11}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{11}}{\lambda_{o}} \right)}}},} & (15) \\{{{where}\mspace{14mu}\Delta_{11}} = {{4n\; L} - {2\left( {{n\; L_{1}} + {n_{s}z}} \right)}}} & \; \\{{{i_{s12}(z)} = {\left( {1 - R} \right)\sqrt{R}\sqrt{I_{r2}{I_{s1}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{12}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{12}}{\lambda_{o}} \right)}}},} & (16) \\{{{where}\mspace{14mu}\Delta_{12}} = {{4n\;\left( {L + d_{1} - d_{2}} \right)} - {2\left( {{n\; L_{1}} + {n_{s}z}} \right)}}} & \; \\{{{i_{s21}(z)} = {\left( {1 - R} \right)\sqrt{R}\sqrt{I_{r1}{I_{s2}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{21}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{21}}{\lambda_{o}} \right)}}},} & (17) \\{{{where}\mspace{14mu}\Delta_{21}} = {{4n\;\left( {L + d_{1} - d_{2}} \right)} - {2\left( {{n\; L_{2}} + {n_{s}z}} \right)}}} & \; \\{{{i_{s22}(z)} = {\left( {1 - R} \right)\sqrt{R}\sqrt{I_{r2}{I_{s2}(z)}}\;{\exp\left\lbrack {- \left( \frac{\Delta_{22}}{L_{c}} \right)^{2}} \right\rbrack}\;{\cos\left( \frac{2\;\pi\;\Delta_{22}}{\lambda_{o}} \right)}}},} & (18) \\{{{where}\mspace{14mu}\Delta_{22}} = {{4n\; L} - {2\left( {{n\; L_{2}} + {n_{s}z}} \right)}}} & \;\end{matrix}$

The star or tree coupler, for example (704) in FIG. 7, can be made sothat I_(r1)=I_(r2). Comparing Equations 15 and 16, it is apparent thati_(s11)(z) and i_(s12)(z) are both LCI signals for I_(s1)(z), and thatthey are exactly equal if d₁=d₂. In other words, when d₁=d₂, not only doi_(s11)(z) and i_(s12)(z) have the same magnitude, but also they occupythe same position in space or time within the overall trace, andtherefore they add up. Similarly, from Equations 17 and 18, the same istrue for i_(s21)(z) and i_(s22)(z) as being LCI signals for I_(s2)(z).Therefore, when d₁=d₂, the LCIs for I_(s1)(z) and I_(s2)(z) are the sumsgiven belowi _(s1)(z)=i _(s11)(z)+i _(s12)(z)=2i _(s11)(z) and i _(s2)(z)=i_(s21)(z)+i _(s22)(z)=2i _(s22)(z)  (19)

Practically the length of the probe branches (708), (710) and (712) canbe made to be as similar as possible. The length adjust elements (730)and (734) that provide the delays d₁ and d₂ and others not shown canalso be used with appropriate voltages applied to the PZT drums tochange or equalize the probe branch lengths.

Speckle noise causes random variations in LCI signals. In ordinaryinterferometers or autocorrelators, the speckle can be averaged out byrepeating the LCI measurements for a given sample arm and adding up theindividual LCI's in time. This signal addition or averaging process isautomatic and at the cost of no extra sampling or processing time in themultiprobe system in versions of the present invention. This isadvantageous and can be applied to a system having any number of probebranches. For a 1:N star coupler, the light in each branch is reduced bya factor of N, but that reduction factor is offset by the fact that eachLCI is increased and averaged by the same factor.

A further randomizing to reduce the speckle noise can be obtained by notmaking d₁-d₂ exactly zero, but rather by providing or maintaining asmall randomized difference (wiggle) between d₁ and d₂. This can be doneby applying a small modulation (with amplitude of the order of one ormore optical wavelengths, i.e., a few microns) on either d₁, d₂, orboth. The modulation to (730) and (734) may be electrically or digitallycontrolled. The frequencies of the wiggles can be the same for all thebranches or can be slightly different for each, but with random startingphase. The frequency is preferably higher than the scan rate of theinterferometer. For example, for a scan time of 50 milliseconds, it issufficient for the wiggling frequency to by higher than 20 Hz. FromEquations 16 and 17, a non-zero value of d₁-d₂ makes Δ₁₂ to be slightlydifferent from Δ₁₁ and causes the exponentials to peak at slightlydifferent locations. Thus, a slight modulation of d₁-d₂ causesi_(s12)(z) to wiggle around a fixed i_(s11)(z) and similarly i_(s21)(z)to wiggle around a fixed i_(s22)(z). This can accomplished by applyingsmall radio frequency voltages to the individual PZT elements to changethe individual lengths by a value of the order of λ_(o). Since the LCIsignal is peak-detected, the phase information is lost by the wigglingprocess and so the speckle noise is averaged out. This capability for“wiggling” the cross-referenced components of an LCI signal provides away to reduce noise in an autocorrelator sensor and can also be appliedto an interferometer having multiple reference arms as illustrated inFIG. 13. Just as for the multiprobe interferometer, i_(s1)(z) andi_(s2)(z) are fully separated in the two-branch autocorrelator system ifL₂>L₁+z_(max).

The multiprobe autocorrelator and interferometric sensors may be used tomeasure and characterize a variety of materials and structures whereflexible fiber scopes cannot be articulated to view nearby or lateralsurfaces. In addition, where there is limited time for scanning or largesurface areas to be scanned, it can be advantageous to use multipleprobes or waveguides and acquire LCI information from a plurality ofprobes in a single scan. The detection of plaque in human arteries is anon-limiting example of an application where narrow passages precludearticulation of a probe to face the walls of the artery and where therecan be a large area that needs to be scanned with a technique havingmicron or submicron resolution. Although reference will be made to theconfiguration and use of versions of the present invention forcharacterizing arteries, other configurations and uses of the sensorsare possible.

FIG. 8( a) illustrates an implementation of the use of the multi-branchprobe sensor to a catheter to be used in an LCI interferometer orautocorrelator which could be used for the detection of vulnerableplaques inside human arteries. Without limitation the same or a similarmulti-branch probe sensor could be used in a borescope, an endoscope,laparoscope, or other inspection device. The inspection device may berigid or it may be flexible and is preferably made from chemicallycompatible and if required a bio-compatible material that is suitablesurface finish for contact with a material or tissue to be examined.Examples of housing materials include but are not limited surgicalsteels, titanium alloys, as well as transparent perfluorinated polymerslike MFA and FEP and combinations of these.

As illustrated in FIG. 8( a), the various sample branches of aninterferometer sensor, for example waveguides (818), (822), and (826),(additional waveguide branches (820), (824), (828), are illustrated inFIG. 8( b)) are brought together and placed inside a housing (858)covering a portion of two or more light propagating probe branches, theprobes capable of guiding light from a low coherence source, coupled towaveguide (810) through a splitter or circulator (not shown), to asample and guiding backscattered light from the sample to a referencesection through a circulator or splitter (not shown) coupled towaveguide (810). Each probe can have an optional adjustable delay, forexample (830), (834), and (838) that can be used with a variable delayin one or more reference-arms of the reference section to provideresolution of two or more low coherence interferometric signals from thesample arms (818), (822), and (826) with a single trace of a referencearm. The housing can be the hollow guide wire of a catheter (858). Thebranches can be coupled to adjustable delays, for example ((830), L₃,τ₃) ((834), L₂, τ₂), and ((838), L₁, τ₁)) (additional delays not shown).The catheter having guidewire (858) and optical head (846) can beinserted in an artery (854) using conventional medical procedures andthe radial light into and backscattered from the sample (866), (870),(others not shown) from optical head (846) of the device used to detecta vulnerable plaque (862) covering a lipid (858) pocket in the artery(854). The number of fiber branches that can be placed inside the hollowguide wire (858) can vary and along with the dimensions of thewaveguides, and will vary depending on the inside diameter of the guidewire or conduit used as a guide. The guide wire is a standard part ofordinary catheters and may chosen to be convenient for thecardiologists.

Rapid signal acquisition and data evaluation capability for longitudinaland radial inspection along a long artery may be achieved in a fewseconds, for example it is expected that a 10 centimeter artery can bescanned in about 10-20 seconds using versions of the present invention.Several methods for deflection of light in the range of about 90° to thedirection of light propagating along axis of the waveguide or pluralityof optical fibers in a fiber bundle can be used in order to “look” atarterial walls. The small size of the waveguide and guide wire alongwith remote location of the reference section and detector can be usedto provide a compact catheter with multiple-branch probes for catheteroperation.

Characterizing arteries or other cavities and conduits for foreignmaterial or growth would benefit from the ability to characterize thesurfaces using radial scans of the cavity surface. For arteries oneobjective is to probe the arterial walls for vulnerable plaques. Thetips of the probes can be made such that the output light propagated bythe waveguides or fiber elements is directed toward the conduit walls orin the present case the arterial walls. As an example, the probe shownin FIG. 8( b) has six fibers ((818)-(828)) pointing in different radialdirections. When this probe is used with an interferometer orautocorrelator with sufficient scanning range, all six LCI profiles canbe obtained in one single trace or scan of the variable delay of thereference (interferometer) or delay compensator(autocorrelator) section,and these profiles separated from each other by virtue of the individualvariable delays imparted to each branch by the methods described videsupra. The artery (854) shown in cross-section in FIG. 8( b) rightillustrates a vulnerable plaque (862) protecting a lipid reservoir (858)just at branch location #3 for probe (818). In FIG. 8( c) an expectedscan for the catheter in the artery (854) is illustrated showing theinterference signals for each of the waveguides. All the profiles whichcorrespond to healthy walls, profiles 1, 2, and 4-6 are shown to beidentical. Profile #3 shows a trace that would be expected tocorresponds to a vulnerable plaque consisting of a layer of calcifiedmaterial (862) and a lipid pool (858) behind it within the arterial wall(854) detected by waveguide (818). The widths of the plaque and lipidregions are measures of their respective thicknesses. The scansillustrated in FIG. 8( c) can be digitized and the various profiles canbe separated and stored in the computer memory for processing. The scansfrom each waveguide in the device may be digitized and compared to eachother or a population of normal artery scans and used to diagnose thepresence or absence, state, extent, or location of a lesion such as avulnerable plaque, a tumor, or damaged tissue. The catheter may then bemoved along the length of the conduit or artery and another radial scantaken and processed.

In another non-limiting example of a catheter illustrated in FIG. 9, thewaveguide fibers (918)-(928) can be assembled around a thin solid andflexible central guide wire (966), such that the fiber assembly itselfcan act as its own guide. The outer surface of the waveguides can beenclosed for example using shrinkable latex or other polymeric andchemically compatible tubing (970). An internal guide wire is usefulwhen a compact sensor is desired. It will be described further inconnection with the geometry of the optical head (946).

As illustrated in FIG. 9( a), the various sample branches of aninterferometer sensor, for example waveguides (918), (922), and (926),(additional waveguide branches (920), (924), (928), are illustrated inFIG. 9( b)) are brought together and placed inside a housing (970)covering a portion of two or more light propagating probe branches, theprobes capable of guiding light from a low coherence source to a sampleand guiding backscattered light from the sample to a reference sectioncoupled via coupler or tree (914) to waveguide (910). Waveguide (910)may be coupled to other elements such as splitters, circulators, orsource light. Each probe is shown having an optional adjustable delay,for example (930), (934), and (938) that can be used with a variabledelay in one or more reference arms of the reference section to provideresolution of two or more low coherence interferometric signals from thesample arms (918), (922), and (926) with a single trace of a referencearm. The housing can be shrinkable latex or other chemically compatibleand optically acceptable material (970). The branches can be coupled toadjustable delays, for example ((930), L₃, τ₃) ((934), L₂, τ₂), and((938), L₁, τ₁)) (additional delays not shown). The device havingguidewire (966) and optical head (946) can be inserted in an artery(954) using conventional medical procedures and the radial light intoand backscattered from the sample (972), (976), (others not shown) fromoptical head (946) of the device used to detect a vulnerable plaque(962) covering a lipid (958) pocket in the artery (954). The number ofwaveguides or fiber branches that can be placed inside the hollow guidewire (970) can vary and along with the dimensions of the waveguides, andwill vary depending on the inside diameter of the guide wire or conduitused as a guide.

Allocating from between 1.5 mm and 2.0 mm per profile (depending onscattering property of sample), a single scan of the inner circumferenceof an artery would require 9 mm to 12 mm of travel and takeapproximately 600 milliseconds for 6 scans excluding rotation of theprobe in the artery. In a system in a version of the present inventionwith a PZT drum and six probes, the same scan may take between 75 and100 milliseconds (ms) to get a trace that contain profiles for all sixlocations. In operation, one inserts the catheter up to a particularlocation in the artery, and after the scan is recorded, the catheter ispulled back (automatically) by about one millimeter and the scan isrepeated until the desired axial length is covered. A non-limitingautomatic pulling rate of about 5 to 10 mm/s can be used. At such arate, and with 100 ms per scan, it would be possible to examine a 10 cmlength of artery in about 20 to 30 seconds with a version of the presentinvention compared to about 2-3 minutes with a probe having only asingle fiber. Advantageously, the shorter scan and pulling time reducesstress on a patient during the procedure. Digitized scans for thevarious waveguide signals at each position along the artery can be madeand stored in the computer memory for processing, analysis, or viewing.

One aspect in the system is that the instrument can be programmed torecognize a disease profile, for example profile #3 illustrated in FIG.8( c). Profile shapes such as interference intensities as a function oflight penetration depth for normal and abnormal conditions (growth,morphology, height, scattering) for a material or tissue can be storedin the memory of a processor that is electrically or optically connectedto the detector. During use, the interference signal from each probe inthe sensor can be compared to a reference material stored trace as wellas an abnormal stored trace. Traces for each of the probes can becompared to stored values or traces for normal tissue, and a indicationprovided to a health care provider when an aberrant trace is detected.Normal tissue traces can be stored and a range or distribution of normaltissue compared to an acquired trace. Changes in the interferenceprofile, for example intensity, shape, or a combination of these outsideof a threshold, from the stored normal profile or from a stored abnormalprofile can be used to indicate the presence of an abnormal condition.The system can also be directed to probe the abnormal position directionand ignore the others by programming the scan start and stop time, thusreducing the scan time in the above case to about ⅙^(th) of the normalscan time and save several seconds from the total probing time. Thealternative, if using a single probe, would require the user to aim theprobe in one direction, then rotate to the next direction until alldirections are probed at a given point along the axis of the artery orother organ or conduit, then pull the catheter and repeat the processuntil the whole length of interest is probed.

Where an interferometer or autocorrelator includes an activating lightsource for photodynamic therapy, and where an abnormal trace isdetected, the activating light may be directed to the probe(s) where theabnormal trace was detected. Alternatively, all of the probes canpropagate the activating light to the region where the abnormal tracewas detected. Photodymanic therapy can be performed and the progress ofthe therapy monitored by the probe after a treatment period.

Another advantage of the multiprobe system is that the cross-referencedprofiles provide a natural averaging process to reduce speckle noise,and that the “wiggling” effect can be used to further reduce the specklenoise. Traditionally performing such averaging required repeating agiven trace several times over a period of time and summing the tracestogether. For diagnosis of a tissue in a patient repeated measurementsprolong the procedure and also introduce variation into the interferencesignal due to changes in patient body position, temperature andpressure. In the multiprobe versions of the present invention, suchaveraging is automatic and can be implemented for both an autocorrelatorand an interferometer.

An optical head that propagates light from the waveguides of the sensorcan be positioned at the distil end of a borescope, endoscope, orcatheter. The optical head can be mounted or formed with the scope orwaveguides and may be used to direct source light from the two or morewaveguides of the sensor to the surface of the conduit or vessel. Theoptical head provides physical and chemical protection to the waveguidesand may incorporate or be adjacent to a conduit in the device thatprovides fluid irrigation to the distil end of the sensor. Light inoptical fibers is guided along the axis of the fiber. To aim the lightat the wall of a conduit, a cavity, or a tissue such as an artery, lightfrom the waveguides or fibers can be directed at an angle from thewaveguide axis to the walls. Depending upon the orientation of thewaveguide, mirror, or fiber end, the illumination of the sample with lowcoherence source light or the collection of backscattered light from thesample may occur at any angle with respect to the axis of the waveguide.For example, for viewing flat surfaces light may be directed andcollected in approximately parallel orientation with respect to thefiber axis as shown in FIG. 7, or the source light may be deflected byan angle to the fiber axis as shown in FIGS. 8-10. For characterizingthe walls of conduits and vasculature the source light can be directedat about 90° toward the wall surface. FIG. 10( a-d) show non-limitingways to achieve this objective. It involves the use of a multi-facetedreflecting surface such as a prism (1006), (1054), (1058), and (1082)that can be for example either polished metal or reflection-coated glasswhich is made to rest on the edges of the waveguides or fibers. Thewaveguides, for example fiber (1018) with core (1016) and clad (1020),with flat polished tips, can be arranged in a circular or othergeometric fashion around a thin guide (1012) or support wire and may beheld together along the guide wire with some cement (for example sprayedon the guide) or epoxy, or some combination of both. In one embodiment,shown in FIG. 10( a), a thin-walled anti-reflection (AR) coated (tominimize reflection) transparent sleeve (1010) that may be glass isplaced around the fibers (1014) and (1018) in the bundle. The spacebetween the guide wire, the fiber, and the prism can be filled withepoxy (1022). The space between the fiber tip, the sleeve, and the prismmay be filled with epoxy FIG. 10( c) (1064) and FIG. 10( d) (1092) or itmay not be filled with epoxy as illustrated in FIG. 10( a) by (1024) andFIG. 10( b) by (1032). If the space is filled with epoxy, it can beplaced for a short time in a vacuum chamber to remove air bubbles. Anadditional dome-shaped mass of epoxy (1026), (1046), (1062), or (1086)can be added to the tip of the assembly in order to prevent scarring theartery or other sensitive tissues/materials during catheter insertion.

The optical heads illustrated in FIG. 10 can be used for theinterferometer multiple probe and the autocorrelator multiple probe.FIG. 10( a-b) illustrate probe head configurations with flat tip fiberwaveguides and reflecting prisms. FIG. 10( a) is for the interferometer,and 10(b) is for the autocorrelator. The difference between theinterferometer and the autocorrelator fiber bundles is that partialreflectors, for example (1034) and (1036), and specific delays (1038)and (1042) are provided in each branch of the autocorrelator probe.These structures for the autocorrelator are illustrated in FIG. 10( b)as indicated by the fiber sections L₁ and L₂, and the partial mirrorsbetween them and the main probe branches (1052) and (1056). Thesebranches can be made by cleaving the main portion at the desired lengthfor the reference light and depositing partial reflectors (1036) and(1034), preferably having about 33% reflection, at the cleaved fiberends, an then fusing the extensions L₁ (1038) and L₂ (1042) to theirrespective branches.

FIG. 10( c) and FIG. 10( d) illustrate alternate heads which can be usedfor protecting the waveguides and directing source light to the sample.In these cases, an epoxy or other optically transparent material in theform of a cap is fashioned over the ends of the waveguides. The epoxy orother material can be ground and polished to remove rough edges anddecrease the difference in size between the outer cap surface and theoutside of the fiber bundle or housing conduit. The cap sides may havean antireflective coating (1066) or (1080) applied to the surface. Theseapproaches provide a reasonably flexible stand-alone catheter which iscapable of providing source light to the sample surface and collectingbackscattered light from the surface. For characterizing vasculature andother narrow conduits with these sensors the cap provides about a 90°angle output and input, for example (1072) and (1096) others not shown,to the axis of the guide wire and the capped device does not damage anartery.

FIG. 11 illustrates additional non-limiting examples for deflectinglight from the waveguide axis to the surface of the sample so thatsource light from two or more waveguides can be used to simultaneouslycharacterize the sample. This can involve grinding and polishing thefiber tips at an angle and depositing a mirror coating on the angledfiber face (1126) in FIG. 11( a) and (1170) in FIG. 11( b). The fiber(1112) includes a cladding (1106) and core (1108). In FIG. 11( a) and(b) the angled fiber tip is illustrated by an approximately 45° anglemade to the surface of the waveguide end. Similar to the previousapproaches, the waveguide or fibers are arranged, preferably in anevenly distributed circular fashion around a thin guide wire (1114) andare held together along the guide wire with cement, epoxy, or both. Inthis case, the low coherence source light is emitted and backscatteredlight collected (1116) and (1118), others not shown, through thecladding (1104) and (1106) of the fibers (1110) and (1112) respectively.The curvature of the fibers can be shaped by laser machining or moldingto act as a convex lens which provides some degree of collimation to thesource light. The wall of the fiber can be AR-coated, for example (1102)and (1122) to minimize reflection. Portions of the space between theguide wire (1114) or (1134) and the fibers can be filled with epoxy(1130) or (1166) or other transparent and chemically inert material. Nospecial treatment is needed for this epoxy, since no light istransmitted through it and there is also no specific alignmentrequirement. It is only sufficient to shape the tip in a shape toprevent damage to the sample or artery during insertion. Theillustration of FIG. 11( a) is used in an interferometric sensor, whileFIG. 11( b) illustrates multiple waveguides (1142) and (1138), othersnot shown, about a guide wire (1134), each waveguide having partialreflectors (1150) and (1152) and angled delay elements (1154) and (1158)which could be used in an autocorrelator. Source light to a sample andbackscattered light collected from the sample (1160) is propagated byfiber (1138), while source light to a sample and backscattered lightcollected from the sample (1176) is propagated by fiber (1142).

With a light source of sufficient intensity, there is no fundamentallimitation to the number of probe branches that can be used. Thus, withenough probes, it is possible to obtain LCI traces around thecircumference of a hollow sample and along its length as well. Thewaveguides or fibers can be distributed about a guidewire or within ahousing, preferably they are distributed to provide substantiallyuniform coverage or sampling of the material to be monitored. In certainapplications, the allowable diameter of the probe may be quite small andthe number of waveguides determined by the allowable size of the probe.More specifically in the case of human arteries, the overall probediameter may be required to be of the order of 0.5 mm or less. FIG. 12shows several configuration for fiber optical probes having 3, 4, 5, and6 branches. These configurations can be obtained by placing the centerof the fibers on vertices of appropriate polygons, circles, or ellipses,and deriving formulas for housing waveguides around them in terms of thefiber clad diameter. FIG. 12( b) illustrates that for the four fibers1202, 1204, 1206, and 1208 with diameter D_(f) in housing 1218, a closepacked configuration for the fibers in this housing configuration themay be achieved using guidewire of diameter D_(g) and housing diameterD_(p). Examples of formulas are given in FIG. 12 and formulas can alsobe derived for the diameter of their supporting guide wire. Althoughpreferred, the various embodiments of the present invention are notlimited to close packed configurations. Also, similar waveguideconfigurations could be derived for irregularly shaped housings. Thenumber of waveguides in the guidewire can also vary with the limit ofthe guidewire diameter and requirements for flexibility of the scope andin particular for a catheter. The diameter for a catheter or borescopeor endoscope can be chose so that it fits through the smallest holeavailable to access the cavity. The borescope diameter preferably clearsthe sides of the hole or organ into which it is inserted. The length ofthe endoscope or borescope can be chosen to penetrate to the greatestdepth required, but not so long as to be unwieldy outside the hole.

The point of borescope, catheter, or endoscope entry and the area to beexamined can be used to modify the direction of view that a reflectingprism can be fashioned to direct the source light. If the subject isstraight ahead of an entry hole an approximately 0° direction-of-viewcan be used and information from two or more fibers used to scan an areaof the surface. If the surface or material to be viewed is very close tothe entry port of the borescope or endoscope, like engine valves near aspark plug hole, a backward-looking prism or suitably angled and coatedoptical fiber may be used. For conduits like an colon or bore of a riflebarrel, a head having a 90° reflecting prism (90 degrees to the axis ofthe fiber or scope axis) can be used.

Field-of-view from the borescope or endoscope time may range from 10 toabout 90 degrees and can be chosen based on the distance from the distalend of the borescope to the subject. A borescope, can have has a verylarge depth of field which can be from infinity down to an centimeter orless. Borescopes and endoscopes of the present invention may be rigid orflexible and can use but are not limited to fiber optic illumination tocarry light from an external light source through a flexible lightguide, then through the borescope, to the distal end. Other sources ofillumination may include activating light for photodynamic therapy, or abulb at the tip or light emitting diodes.

FIG. 12, D_(p), D_(f), and D_(g) represents the diameter of probe (thecircle around the fibers) or sample arm, the diameter of the fiber, andthe diameter of the guide wire, respectively. Various non-limitingconfigurations for a typical fiber having 125-micron clad diameter areillustrated in Table 1.

TABLE 1 Relation of probe and guide wire diameters to fiber diameter.Application to fiber with D_(f) = 125 micron Number of Overall probediameter probe branches D_(p) (and actual value) Guide wire diameterD_(g) 3 D_(p) = 2.15 D_(f) (269 μm) D_(g) = 0.15 D_(f) (19 μm) 4 D_(p) =2.41 D_(f) (301 μm) D_(g) = 0.41 D_(f) (51 μm) 5 D_(p) = 2.7 D_(f) (338μm) D_(g) = 0.7 D_(f) (88 μm) 6 D_(p) = 3.0 D_(f) (375 μm) D_(g) = 1.0D_(f) (125 μm)

In an autocorrelator in versions of the present invention, the sensinglight in a given branch can interfere with the reference lights fromother branches to provide several replica of the LCI signal for thatparticular branch. These signals can be made to superimpose byequalizing the various paths, which causes the various replicas add tothe self-referenced LCI to increase the total signal or provide anaverage signal without the need to repeat scans. A small modulation canbe added to vary d₁-d₂ so that it is not zero, modulating them about theself-referenced signal, and achieve noise reduction by averaging thenoise out. The same result can be achieved with an interferometer by theuse of two or more reference arms.

FIG. 13 shows the interferometer previously described in FIG. 4, butwith the addition of an second reference arm (1314) having variabledelay (1342) of L_(b), τ_(b) and adjustable mirror (1332) in addition tothe first reference arm (1310) having variable delay (1328) of L_(a),τ_(a) and adjustable mirror (1330). Low coherence light from source(1306) with optional isolator (1308), propagates through waveguide(1312) to splitter (1316). A portion of the source light from thesplitter enters the reference arms through waveguide (1324) and theother portion enters the tree (1344) through waveguide (1348) where itis propagated to the sample arms (1318), (1322) and other arms (1340)(not shown). Sample arm (1318) has variable delay (1334) of L₁, τ₁ andsample arm (1322) has variable delay (1336) of L₂, τ₂, (the delays ofthe other arms are not shown). Source light backscattered from thesample (1338) is propagated by the sample arms and combined with thereference light and propagated to the detector through waveguide (1320)coupled to splitter (1316). The interference measured at the detectorcan be processed further by processor (1356).

The analysis for the sensor of FIG. 13 can be done for an arbitrarynumber of reference and sensing arms, but two reference arms (1310) and(1314) and sensing or sample arms (1318), (1322), and others (1340) areused to illustrate the operation in this case. The sensing electricfields can be designated as E_(s1) and E_(s2) as before, and the tworeference fields designated as E_(ra) and E_(rb), respectively. Carryingthe analysis and selecting the detector current components which providematching path lengths, for example path length differences which can bemade equal to zero, yields the following four signal components:i_(s1a), i_(s1b), i_(s2a), and i_(s2b) as shown in equations (20)-(23)

$\begin{matrix}{{{i_{s1a}(z)} = {\sqrt{I_{ra}{I_{s1}(z)}}{\exp\left\lbrack {- \left( \frac{\Delta_{1a}}{L_{c}} \right)^{2}} \right\rbrack}{\cos\left( \frac{2{\pi\Delta}_{1a}}{\lambda_{o}} \right)}}},{{{where}\mspace{14mu}\Delta_{1a}} = {{nL}_{a} - \left( {{nL}_{1} + {n_{s}z}} \right)}}} & (20) \\{{{i_{s1b}(z)} = {\sqrt{I_{rb}{I_{s1}(z)}}{\exp\left\lbrack {- \left( \frac{\Delta_{1b}}{L_{c}} \right)^{2}} \right\rbrack}{\cos\left( \frac{2{\pi\Delta}_{1b}}{\lambda_{o}} \right)}}},{{{where}\mspace{14mu}\Delta_{1b}} = {{nL}_{b} - \left( {{nL}_{1} + {n_{s}z}} \right)}}} & (21) \\{{{i_{s2a}(z)} = {\sqrt{I_{ra}{I_{s2}(z)}}{\exp\left\lbrack {- \left( \frac{\Delta_{2a}}{L_{c}} \right)^{2}} \right\rbrack}{\cos\left( \frac{2{\pi\Delta}_{2a}}{\lambda_{o}} \right)}}},{{{where}\mspace{14mu}\Delta_{2a}} = {{nL}_{a} - \left( {{nL}_{2} + {n_{s}z}} \right)}}} & (22) \\{{{{i_{s2b}(z)} = {\sqrt{I_{rb}{I_{s2}(z)}}{\exp\left\lbrack {- \left( \frac{\Delta_{2b}}{L_{c}} \right)^{2}} \right\rbrack}{\cos\left( \frac{2{\pi\Delta}_{2b}}{\lambda_{o}} \right)}}},{{{where}\mspace{14mu}\Delta_{2b}} = {{nL}_{b} - \left( {{nL}_{2} + {n_{s}z}} \right)}}}{{{{where}\mspace{14mu} I_{ra}} = E_{oa}^{2}},{I_{rb} = E_{ob}^{2}},{I_{s1} = E_{s1}^{2}},{I_{s2} = {E_{s2}^{2}.}}}} & (23)\end{matrix}$

There is an extra DC term (included because its path difference can bemade equal to zero) which carries no information:

$\begin{matrix}{{I_{ab} = {\sqrt{I_{ra}I_{rb}}{\exp\left\lbrack {- \left( \frac{\Delta_{ab}}{L_{c}} \right)^{2}} \right\rbrack}{\cos\left( \frac{2{\pi\Delta}_{ab}}{\lambda_{o}} \right)}}},{{{where}\mspace{14mu}\Delta_{ab}} = {n\left( {L_{a} - L_{b}} \right)}}} & (24)\end{matrix}$

Comparing these equations, it can be shown that i_(s1a)(z) andi_(s1b)(z) are both LCI signals for I_(s1)(z), and that i_(s2a)(z) andi_(s2b)(z) are LCI signals for i_(s2)(z). Therefore, they can becombined, respectively, to give i_(s1)(z) and i_(s2)(z), wherei _(s1)(z)=i _(s1a)(z)+i _(s1b)(z) and i _(s2)(z)=i _(s2a)(z)+i_(s2b)(z)  (25)

In particular, the two terms in i_(s1)(z) and the two terms in i_(s2)(z)add up exactly if L_(a)=L_(b). Furthermore, if a slight random timemodulation at a frequency higher than the scan rate is imparted toL_(b), then i_(s1b)(z) will wiggle around i_(s1a), and i_(s2b) willwiggle around i_(s2a). The two components of each signal will wiggle inopposite directions about each other if the modulation imparted to L_(a)is the opposite of that imparted to L_(b). In general, any variation ofL_(a) and L_(b) are allowed. Again, since the LCI signal ispeak-detected, the phase information is lost by the wiggling process andthe speckle noise is averaged out.

EXAMPLE 1

This prophetic example illustrates how an version of the presentinvention can be used for detecting plaque within the coronary or otherpatient vasculature. The apparatus and techniques could also be appliedto characterizing lesions in other body lumens which are associated withvarious disease conditions. The methods and apparatus can be implementedwithin the body lumen to identify diseased tissue or monitor the courseof treatment for a particular condition. The apparatus is able tointerrogate the body lumen over a relatively long distance tocharacterize the tissue in an efficient fashion by providinginterferometric information on the tissue from multiple probes in asingle sweep of a variable delay of the apparatus.

Coronary artery disease resulting from the build-up of atheroscleroticplaque in the coronary arteries is a leading cause of death. Thebuild-up of plaque causes a narrowing of the, artery, commonly referredto as a lesion, which reduces blood flow to the myocardium (heart muscletissue). Myocardial infarction can occur when an arterial lesionabruptly closes the vessel, causing complete cessation of blood flow toportions of the myocardium. Even if abrupt closure does not occur, bloodflow may decrease resulting in chronically insufficient blood flow whichcan cause significant tissue damage over time.

Plaques which form in the coronaries and other vessels compriseinflammatory cells, smooth muscles cells, cholesterol, and fattysubstances, and these materials are usually trapped between theendothelium of the vessel and the underlying smooth muscle cells. It isexpected that these lesions will have optical properties that differfrom the surrounding healthy tissue. The difference in the opticalproperties may be detected and characterized by a change in incidentsource light of one or more wavelengths backscattered from the sample.Depending on various factors, including thickness, composition, and sizeof the deposited materials, the plaques can be characterized as stableor unstable. The plaque is normally covered by a cap and/or anendothelial layer as illustrated in FIG. 8( b). When the cap and/orendothelial layer is disrupted, the ruptured plaque releases highlythrombogenic constituent materials which are capable of activating theclotting cascade and inducing rapid and substantial coronary thrombosis.Such plaque is referred to as unstable or vulnerable, and the resultingthrombus formation can cause unstable angina chest pain, acutemyocardial infarction (heart attack), sudden coronary death, and stroke.Based upon the light backscattered source light of one or morewavelengths from the artery walls, the sensor of the present inventionmay be used to determine the location, chemical and physical properties,and nature of the lesion in an artery. This information can be used tofacilitate determining whether the plaque is stable or unstable, and maybe used to treat and monitor the treatment.

As shown in FIG. 14, a sensor for characterizing the artery can be madeby coupling three waveguides (1408), (1428), and (1442) using treecoupler (1414), each waveguide having an adjustable delay such as(1410), (1416), (1420) the waveguides located within a housing (1418).The pathlength of the three waveguides differ from each other and areless than the pathlength of the delay compensator section. Thewaveguides a can be coupled to a low coherence light source(not shown)and a delay compensator section through a circulator (1426). The delaycompensator section (1430) includes waveguide (1444) and an adjustabledelay (1464) and waveguide (1448) and adjustable delay (1458). Probewaveguide (1428) is shown with partial reflector (1422) and delayelement (1424); the other probe arms (1408) and (1442) also includethese elements. The delay arms (1444) and (1448) are coupled to Faradayreflectors (1446) and (1450) respectively. The sensor waveguides areable to propagate light input (1412) from one or more low coherencesources (not shown) through waveguide (1404) coupled to the circulator(1426) and to a sample tissue such as an artery (1454) through probewaveguides (1408), (1442), and (1428). The low coherence light isdirected to the surface of the sample artery (1454) and backscatteredlight from the surface collected by the one or more probes (1438). Theseprobe waveguides are able to propagate backscattered source light fromthe sample (1438), to an interferometer or delay compensator section(1430) through waveguide (1432) and splitter (1436). The waveguides(1408), (1442), and (1428) are configured such that interference betweenthe backscattered light from the sample (1458) and reference light fromthe probe arms is separately detected by a detector, not shown, whichcan be coupled to the splitter (1436) through waveguide (1452). Thethree waveguide interference signals are detected during a single sweepof the delay compensator section adjustable delays ±L or ±r.

The artery or other tissue (1454) can be characterized by contacting itas illustrated in FIG. 14. The sensor probe and reference section arecoupled together and each probe arm has an adjustable delay that can beused to adjust the delay of the probes (1408), (1442), and (1428) toaccount for index of refraction (n) changes, light penetration depth(z), and keep the length of the probes different from one another andwithin the adjustable delay of the delay compensator section.Interference between backscattered source light from the sample (1454)detected by the three probe arms combined with reference light from theprobe arms interfere after compensation by the delay compensator sectionand the interference signal measured at a detector. The interferencesignals are resolved during a single trace of the reference sectionwhere a trace is at least the sum of the nL's for each probe and nz foreach probe.

The interference signal determined for each probe arm could becompletely separated from the LCI signal from the other probe arms or itcould be less than completely separated. Adjustment to the probe armdelays can be made to achieve complete separation. In FIG. 14, theinterference detected for each of the three probes provides acharacterization of the artery in the three sections. A change in theinterference measured by any of the probes that differs from one or moreof the other probes or from a reference trace from a healthy artery isexpected to indicate a change in the health or state of the tissue. Fora patient at risk for having lesions based upon past medical diagnosis,previous medical condition, or present health as determined by aphysician, the presence of an abnormal interference pattern from a scanmay indicate the presence of a diseased tissue such as a plaque in theartery. By using one or more low coherence light sources with differentcenter wavelength, a spectroscopic analysis of a tissue or sample can beperformed and the trace as a function of wavelength determined. It isexpected that because the penetration and backscattering of lowcoherence light varies with wavelength and tissue type, variations inLCI signals between normal and diseased tissue can be readily detected.Other methods may be used to confirm the presence of a diseased tissuelike a vulnerable plaque and support that a particular trace structureindicates the presence of a diseased tissue like a vulnerable plaque.

This example illustrates how detecting the interference between lowcoherence light backscattered from a sample that is propagated in two ormore adjustable waveguides can be combined with low coherence light froma delay compensator section having an adjustable delay so that a singlesweep of the reference section yields interference signals that areresolved and provide information about a tissue.

EXAMPLE 2

This prophetic example illustrate how a sensor of the present inventionmay be used in photodynamic therapy to treat and monitor a lesion.

Photodynamic therapy (PDT) is effective in destroying diseased tissueand tumors using light that is absorbed by a photoreactive agentadministered to the patient. The photoreactive agent is selectivelypreferentially absorbed by or linked to the abnormal or diseased tissueand has a characteristic absorption wavelength or absorption band thatactivates the agent. When activated by the light, the photoreactiveagent can produce compounds that destroy the abnormal tissue. The depthof light penetration, and consequently of the tissue necrosis, is afunction of light wavelength, and is typically less than one centimeter.

PDT may be administered locally to a site in or on a patient using lightfrom an external light source such as a laser that is coupled to aplurality of optical fibers or waveguides. The waveguides that propagatethe light to the site can be housed in a catheter or endoscope and thesesame waveguides can also be the sample arms of an autocorrelator orinterferometric sensor. Alternatively, the catheter or endoscope housesseparate sets of waveguides—one set to propagate light for photodynamictherapy to a site of the patient's body to be treated, another set ofwaveguides acting as sample or probe arms for the sensor.

The sample arms of an autocorrelator or interferometric sensor can beused to locate a lesion and can be used to monitor the progress of thephotodynamic therapy including damage to abnormal and normal tissue.Damage to normal tissue can occur during PDT due to the non-homogeneousdistribution or non-selective binding of the photoreactive agent withinan abnormal tissue and within the surrounding normal tissue.

For example, a catheter that houses two or more sample arms can beinserted within the diseased tissue at a site as illustrated in FIG. 15.In this non-limiting example, light from multiple wavelength sources(1510) λ₁, (1512) λ₂, and (1514) λ₃ can be multiplexed using wavelengthdivision multiplexer (1522) coupled into circulator (1530). Light foractivating an agent from source (1516) λ₄ may be coupled through wavedivision multiplexer (1522) into the circulator (1530) or one of the lowcoherence sources may act as an activating light. Alternatively, a lightsource can be disposed outside of the patient's body (not shown) whileadministering the light therapy and a catheter or endoscope includingone or more sample arms (1540), (1542), or (1544) at or near the site tomonitor the photodynamic therapy. Where the light source is locatedoutside of the patient's body, and if necessary, the source is selectedto have wavelengths and intensity sufficient to penetrate normal tissueoverlying the internal treatment site to reach the diseased tissue.

Photodynamic therapy can include the acts of activating a photosensitiveagent administered to the patient and monitoring the normal and diseasetissue at the site where the light is directed with a sensor or catheterof the present invention having two or more sample or probe arms. Forexample, activating light from source (1516) can be directed through WDM(1522), through circulator (1530) and propagated into tree (1534) whereit is divided into waveguides (1540), (1542), and (1544) and directed tothe distal end of a catheter adjacent tissue as illustrated in FIG. 15.Alternatively, the activating light may be directed to a single one ofthe waveguides (1540), (1542), and (1544) using an optical switch (notshown). Each of the probe arms can have an adjustable delay (1556),(1560), and (1562), and each includes partial reflector such as (1566)and delay element (1564). After a period of exposure of the site to theactivating light from source (1516), the source can be turned off andthe site characterized by directing low coherence light from one or moresources like (1510), (1512), or (1514) to the sample arms of the sensorin the catheter housing (1552). A phototherapy method according toanother aspect of the invention includes the acts of identifying atissue in need of photodynamic therapy using a sensor of the presentinvention having one and preferably two or more sample arms and one ormore reference arms, and activating a pharmaceutical compositionadministered to the patient that can be activated by light flux and thatleads to necrosis of the identified tissue in response to the lightflux. The method can further include the act of interferometricmonitoring of the progress of the photodynamic therapy. Light flux foractivating the pharmaceutical can be applied externally to the patient,or it can be applied to any tube-like anatomical organ, duct, or cavity,including, but not limited to, esophagus, blood vessels, lymphatics,urethra, lung/trachea, cervix, oral cavity, and rectum of the patientthrough a catheter. The catheter, which may be introduced into theconduit or vessel directly, or by penetration through tissue, such asmuscle tissue, as by means of a needle, preferably is a catheter havingone or more, and even more preferably two or more sample arms of aninterferometer or autocorrelator of the present invention. Based on theinformation received from the sensor, the therapy may be modifiedincluding but not limited to changing the intensity or flux of the lightapplied to the tissue and or changing the duration of the light appliedto the site.

The results of this example show that versions of the present inventionmay be used to identify a tissue in need of treatment, may be used toprovide treatment, and can be used to monitor the progress of a therapy.

EXAMPLE 3

This example illustrates a method for characterizing a material samplethat includes contacting the material with a sensor having two or moreprobes or sample arms and a delay compensator or a reference sectionrespectively. Each probe arm can include an adjustable delay, the probearms and reference section configured such that an interference betweenbackscattered source light from the sample for two or more probe armsand reference light occurs and is detected during a single trace of thedelay compensator or reference section.

Preferably the interference signal for the two or more probe or samplearms are at least partially separated from each other. The material canbe a tissue where characterization includes the detection of a diseasestate of the tissue. Preferably the disease state being characterized isa vulnerable plaque.

EXAMPLE 4

This prophetic example illustrates a method of making a sensor inversions of the present invention;

The sensor can be made by coupling two or more waveguides sample armsand one or more reference arms having adjustable delays, the waveguidesable to propagate light from a low coherence source to a sample and ableto propagate backscattered source light from the sample. The waveguidescan be configured such that interference between the backscattered lightand reference light for two or more waveguides are separated from eachother during a single sweep of a variable delay of a reference sectionor a single sweep of adjustable delay of a delay compensator section.

Backscattered light collected from two or more probes or sample arms maybe coupled to a reference section or to a delay compensator section.Interference between the backscattered light and reference light ismeasured by a detector that can be coupled to a splitter propagatinglight from reference arm or the delay compensator. The interferencemeasured by a detector can be sent to a processor, the detector outputis proportional to the interference and a signal or display provided bythe processor.

Although the present invention has been described in considerable detailwith reference to certain preferred embodiments thereof, other versionsare possible. Therefore the spirit and scope of the appended claimsshould not be limited to the description and the preferred versionscontain within this specification.

1. A sensor comprising: at least one light source: two or more samplearms, each sample arm having a different pathlength coupled to the atleast one light source, wherein light from the at least one light sourceis propagated through the two or more sample arms to a sample andbackscattered light is collected from the sample and propagated backthrough the two or more sample arms; one or more reference arms, eachhaving an adjustable delay to the at one light source, wherein lightfrom the light source is propagated through the one or more referencearms and reflected back to through the one or more reference arms tomake reference light and wherein each adjustable delay is capable ofmodifying the pathlength of a reference arm to match the pathlength ofeach of the two or more sample arms; a coupler configured to combinebackscattered light from the two or more sample arms and reference lightfrom the one or more reference arms to produce an interference signal;and a detector coupled to the coupler that detects the interferencesignal and produces an output signal; and a processor coupled to thedetector that resolves the output signals from the detector in a singletrace wherein a single trace represents a sweep of the adjustable delayof the one or more reference arms and includes resolved interferometricsignals for each of the two or more sample arms.
 2. The sensor of claim1, wherein each of the two or more sample arms include a variable delay.3. The sensor of claim 1, wherein the at least one light source is a lowcoherence light source.
 4. The sensor of claim 1, wherein the processorproduces an output proportional to the interference between thebackscattered light and reference arm light for each of the two or moresample arms.
 5. The sensor of claim 1, further comprising a housingcovering at least a portion of the two or more sample arms and bringingthe two or more sample arms together.
 6. The sensor of claim 5, whereinthe housing is a catheter.
 7. The sensor of claim 5, wherein the housingis a guidewire.
 8. The sensor of claim 1, further comprising anactivating light source.
 9. The sensor of claim 1, further comprising arandom time modulator coupled to the adjustable delays of the one ormore reference arms to average out noise.
 10. The sensor of claim 1,wherein the adjustable delay modifies the pathlength of the referencearm by means selected from adjusting the physical length of thereference arm, adjusting the optical length of the reference arm,adjusting the refractive index of the reference arm, providing anoptical delay and combinations thereof.
 11. The sensor of claim 1,wherein the adjustable delay is selected from a movable mirror, apiezoelectric stretcher and combinations thereof.
 12. The sensor ofclaim 1, further comprising one or more devices selected from splitters,couplers, circulators, reflectors, Faraday rotators, lenses,multiplexers and combinations thereof.
 13. The sensor of claim 1,configured to make radial scans of a cavity.
 14. The sensor of claim 13,wherein the cavity is an artery.
 15. The sensor of claim 1, furthercomprising an optical head that directs light from the two or moresample arms toward the sample.